Lectures Flashcards
3 components of Communication Systems in body
- Nervous system
- Endocrine system
- Immune system
three most important communication systems in body
these symptoms are interconnected
forms of communication between nervous system and endocrine system
- hormones
- neurotransmitters
forms of communication between endocrine system and immune system
- hormones
- cytokines
forms of communication between nervous system and immune system
- cytokines
- neurotransmitters
nervous system splits into…
central nervous system and peripheral nervous system
central nervous system
division of the nervous system
structures encased in bone
- brain (cranium)
- spinal cord
peripheral nervous system
division of the nervous system
- autonomic system
- somatic system
autonomic nervous system
responsible for INVOLUNTARY control of the body
somatic nervous system
responsible for CONSCIOUS PERCEPTION and VOLUNTARY MOTOR RESPONSES
autonomic system splits into…
- sympathetic
- fight or flight - parasympathetic
- rest and digest
what kind of neurons for parasympathetic system?
cholinergic
what kind of neurotransmitter for sympathetic system?
norepinephrine
somatic nervous system
subdivision of peripheral nervous system
allows you to move and control muscles
feeds info from 4 senses to brain
2 pathways
four senses whose info are carried by the somatic NS
smell
sound
taste
touch
somatic NS: two pathways of info
- afferent
- efferent
afferent pathway
carries info from SENSORY receptors to the CNS
efferent pathway
carries MOTOR INFO away from the CNS to the MUSCLES/GLANDS
classical definition of behaviour
behaviour results from 3 interacting components
hormones can effect which of the components of behaviour?
all three (input, CNS or output)
3 interacting components which result in behaviour
- input system/sensorial stimulus (internal or external)
- central NS
- output system/peripheral NS (effectors)
superior
above
inferior
below
rostral
front
caudal
back
anterior
in front
posterior
behind
dorsal
back
ventral
front/belly
3 axes we use to slice brain
- coronal
- sagittal
- horizontal
coronal slice
divides front and back of brain
sagittal slice
splits brain into the two hemispheres (along the longitudinal fissure)
horizontal slice
divides top and bottom of brain
entire central nervous system comes from what in the fetus?
neural tube
entire brain comes from this tube
neural tube develops when
3 weeks
3 vesicles of the neural tube
forebrain
midbrain
hindbrain
later on in development, the forebrain divides into…
telencephalon (cerebrum)
diencephalon (lower structures)
telencephalon is composed of…
- cortex
- limbic system
- basal ganglia
diencephalon
- thalamus
- hypothalamus
most of the brain is composed of the…
cerebral cortex
cerebral cortex functions
consciousness, thought, emotion, reasoning, language, memory
cerebral cortex is subdivided into…
4 lobes
frontal, temporal, parietal, occipital
corpus callosum
connects hemispheres of brain
cortex is how thick
3 mm
covers both hemispheres
cortex is composed of…
grey matter
bodies of the neural cells
white matter
axons
means that all the grey matter (cell bodies) are connected all over the brain by the white matter (axons)
DTI
uses water to show the neuron connections and their activity
frontal lobe 4 main functions
- reasoning/executive functioning (PFC)
- motor control (motor cortex)
- emotion
- language (Broca’s area)
where is the motor cortex?
PFC
precentral gyrus
Broca’s area
essential for language production
in frontal lobe
early evidence of importance of frontal lobe in behaviour regulation
case of Phineas Gage
Phineas Gage
railroad construction accident survivor
large iron rod was driven completely through his head
where were the lesions in Phineas Gage’s brain?
widespread lesion of LEFT FRONTAL LOBE
reported effects of Gage’s lesions
affected personality and behaviour
parietal lobe
processes sensory info of the body
contains SOMATOSENSORY CORTEX
somatosensory cortex alternative name
postcentral gyrus
somatosensory cortex is organized in what manner?
topographically
ie. cortical homunculus
temporal lobe main function, and secondary ones
main: processing auditory signals
secondary: learning, memory, language, integrates info from other brain regions
occipital lobe
at back of head
interprets VISUAL info
also involved in balance - cerebellum
boxing anecdote occipital lobe
illegal in boxing to punch at the back of the head
because it can cause loss of vision
subcortical regions
regions other than the frontal, parietal, temporal, and occipital lobes are SUBCORTICAL
4 subcortical regions
- amygdala (fear/anxiety)
- hippocampus (learning/memory)
- hypothalamus (homeostasis - connection with endocrine system)
- thalamus (relay centre of brain)
limbic system is composed of…
amygdala, hippocampus, hypothalamus, thalamus
amygdala has lots of receptors for…
cortisol
reacts to stress
limbic system is where our ____ originate
initial emotional responses
limbic system is located where
between brainstem and neocortex
acts like a bridge between these two areas
has a consensus been reached on what parts of the brain compose the limbic system?
not really
but it’s agreed upon that the amygdala, hippocampus, thalamus and hypothalamus are part of it
what is the structure behind our body FEELING the emotions that we experience?
hypothalamus
limbic system in reaction to scary movie
watching movie
- hypothalamus receives a signal from the amygdala that something frightening is being presented
- hypothalamus triggers the fear/fight or flight response
“the master regulator of the endocrine system”
the hypothalamus
if hippocampus is damaged…
can’t convert STM to LTM (anterograde amnesia)
people feel less fear, hyper-sexuality and mellowness
SM’s amygdala was damaged…
and she couldn’t feel fear as a result
case of HM
suffered from seizures
removed hippocampus in attempt to treat it
function of hippocampus was unknown at the time
seizures stopped, IQ improved
ONE PROBLEM: his memory was gone
- lost most memories of past
- short term mem couldn’t be consolidated
couldn’t form new memories
but could keep it in working memory
before HM, memory was thought to be…
monolithic and stored in the same place in the brain
HM paved way to distinction between STM and LTM
and idea that diff mems are stored in diff areas
hippocampus main function
memory consolidation
STM to LTM
procedural memory relies more on which two structures?
- basal ganglia
- cerebellum
^these two structures were both intact in HM’s brain
2 main parts of the midbrain
substantia nigra
ventral tegmental area
(located deep within the brain)
midbrain is responsible for what three main things?
mood, reward and addiction
hindbrain 3 parts
- medulla
- pons
- cerebellum
medulla
controls automatic processes of ANS
blood, breathing, heart rate
pons
connects hindbrain to rest of brain
means “bridge”
cerebellum
receives msgs from joints and ear structures
controls balance
some procedural memory
two types of neuronal cells
- neurons
- glial cells
glial cells comes from what word
Greek word for “glue”
glial cells were initially thought to only…
- hold neurons in place
- act as supportive cells
now we know that glial cells have a variety of functions, such as…
- providing support to neurons
- repairing damage
- fighting infections
- influencing neurotransmission
3 types of glial cells
- microglia
- oligodendrocyte
- astrocyte
microglia
immune response
homeostasis
supporting neuronal function
oligodendrocyte
produce myelin sheaths that wrap around axons
nurturing and sustaining the environment around axons
astrocyte
neural support
repair damage
regulate neuronal communication
in PNS, oligodendrocytes are called…
schwann cells
in PNS, astrocytes are called…
satellite cells
neurons are _______ cells
excitable
can be excited in certain situations
dendrite
serve as input sites where SIGNALS ARE RECEIVED from other neurons
are different at diff ages
old people have less, and shorter, dendritic spines
stress and dendrites
stress can reduce number of dendritic spines
each dendritic spine is postsynaptic to…
one or two axon terminals
intellectual disability and dendritic spines
spines have diff (abnormal) formations in intellectual disabilities
axons
longest projections from the soma
end at multiple terminal buttons
terminal buttons
where the signal (action potential) finishes
where the neuron communicates with another neuron/other cells
soma
central part of neuron
soma contains…
watery fluid called CYTOSOL
cytosol
watery fluid inside the cell
salty, potassium rich solution
cytosol is separated from the outside of the cell by the…
neuronal membrane
membrane-enclosed structures within the soma
organelles (ribosomes, proteins)
cell body of neuron contains SAME organelles found in all animal cells
nucleus
produces proteins
spherical, centrally located part of the neuron cell
nucleus is contained within a…
DOUBLE MEMBRANE called the nuclear envelope
nuclear envelope
the double membrane that contains the nucleus
it’s perforated by POREES
some hormones act within the neuron nucleus and…
have TRANSCRIPTIONAL properties
nucleus and hormones
some hormones affect the nucleus
bind to receptors
GENE TRANSCRIPTION to create proteins
gene transcription
- RNA molecules are synthesized by RNA polymerase
- then processed into mRNA to carry genetic instructions for protein assembly from nucleus to cytoplasm
- transcription is initiated at promoter region of gene and stopped at terminator region
- initial RNA must be spliced to remove the introns that don’t code for protein
- then are exported from nucleus
membrane
- serves as BARRIER to enclose the cytoplasm inside the neuron
- excludes certain substances that float in the fluid that bathes the neuron
- various types of proteins are embedded within the neuron cell membrane
4 proteins embedded within the membrane of neurons
- ion channels
- transporters
- receptors
- enzymes
ion channels
allow the passage of ions (ie. sodium, potassium, calcium) in and out of the cell
facilitates nerve impulse transmission
transporters
assist in the movement of molecules and ions across the membrane
receptors
bind to specific neurotransmitters or signalling molecules, initiating cellular responses
enzymes
catalyze specific chemical reactions crucial for cellular functions
function of neurons cannot be understood without understanding structure and function of…
membrane and its associated proteins
membrane is important in maintaining difference in…
electrical charge
resting membrane potential
cell is at rest
not generating impulses
inside the cell = negative
outside the cell = positive
how do neurons maintain the difference in electrical charge?
ion channels
sodium, potassium and chloride
sodium and potassium = positively charged
chloride = negatively charged
sodium-potassium pump
uses energy (via ATP -> ADP)
to constantly pump 3 sodium ions OUT of the cell
and 2 potassium ions INTO the cell
uses energy to constantly maintain the difference in electrical charge
sodium-potassium pump helps to keep the electrical charge inside the cell…
less positive than the electrical charge outside the cell
so more negative inside the cell
what percentage of brain’s energy is used to maintain the electrical diff for neurons?
60-70%
very energy-demanding
what happens when neuron receives a stimulus?
rapid reversal of the resting state
the membrane becomes positively charged
the _______ and _______ of action potentials constitute the code used by neurons to transfer info from one location to another
FREQUENCY and PATTERN
in resting state, charge of inside of cell is
-70 mV
while the outside is positive
when neuron receives stimulus, what channels open?
sodium channels
because sodium ions are more concentrated OUTSIDE the cell, they flow inside the cell (concentration gradient)
because sodium is positive, the membrane DEPOLARIZES
repolarization
cell depolarizes with the stimulus
sodium ions enter the cell and make the inside positively charged
reaches a peak of 50 mV
then there is a process of REPOLARIZATION where the neuron returns to resting state
during depolarization, what peak charge does the inside of the cell reach?
50 mV
hyperpolarization
when neuron is too negative
cannot depolarize/fire in this state
refractory period
what channels open during repolarization?
potassium channels
potassium leaves the cell (because of concentration gradient) until it reaches its resting state of -70 mV once more
how does neuron return to resting potential after firing?
sodium-potassium pump
brings 2 potassiums into cell
brings 3 sodiums out of cell
now ready for another action potential
unmyelinated versus myelinated axons
myelinated with nodes of ranvier = faster transmission
signal/action potential jumps from node to node
5 action potential properties
- all same size
- all same duration
- don’t diminish as they move down the axon
- frequency and pattern of action potentials constitute the code used by neurons to transfer info from one location to another
- very rapid - 100 times faster than blink of an eye
how long do action potentials last?
about 2 milliseconds
at the axon hillock…
action potentials undergo summation
potentially is enough to generate the release of neurotransmitters
neural firing chain of 6 events
- neurotransmitter release
- receptor binding
- ion channels open/close
- conductance change causes current flow
- postsynaptic potential changes
- postynaptic ions excited or inhibited
ionotropic vs metabotropic
ionotropic: ligand-gated ion channels
metabotropic: G-protein coupled receptors
4 NT pathways
DANS
- dopamine
- acetylcholine
- norepinephrine
- serotonin
NTs occur in specific pathways, aren’t just randomly distributed across the cortex
what creates the potential in a cell?
the -70 mV difference between the inside and the outside of the cell
this difference in charge creates the potential for action and for rest as well
communication between neurons and glands is very _____, while communication between glands is very _____
fast
slow (because the hormone must travel through the bloodstream to reach the target)
behavioural endocrinology is the study of…
scientific study of the BIDIRECTIONAL interactions between hormones and behaviour
hormones can affect behaviour, and behaviour can influence hormones
3 things that hormones affect which indirectly impact behaviour
they affect individuals’:
- sensory systems
- integrators
- effectors (output systems)
^all three of these are important for behaviour, and hormones affect all of them
hormone
organic chemical messenger
released from endocrine cells
travels through blood system to interact with cells via very specific receptors
endocrine glands
ductless glands from which hormones are released into the blood stream
release hormones in response to specific physiological signals
hormones do what to influence probability of behaviour
- they change gene expression
- or they change rate of cellular function
these two things affect behaviour by increasing the probability that a given behaviour will occur in the presence of a specific stimulus
endocrine cells versus endocrine glands
endocrine cells: ie. fat
- fat releases hormones
endocrine glands:
- produce and release hormones
- can be released by direct innervations or if something binds to the gland (cascade)
the effects of hormones are notable not only in behaviour…
but also in several human ATTRIBUTES and CHARACTERISTICS
3 examples of how hormones affect other human attributes and characteristics
- Lance Armstrong admittedly used EPO, blood transfusions, testosterone and corticosteroids when competing
- Testosterone treatment
- Messi had Growth Hormone Deficiency (GHD) and received GHD injections
testosterone causes…
gain of body mass
higher levels of aggression/paranoia
messes with feedback mechanisms between communication between brain and testes
historical roots of behavioural endocrinology
remarkably multidisciplinary from the very beginning
relationships among endocrine glands, their hormone products and behaviour have been implicitly recognized for centuries
example of relationship between endocrine glands, their hormone products and behaviour
male sex organs (testes) produce and secrete a hormone called testosterone that influences sexual behaviour, aggression, territoriality, as well as other behaviours that differentiate males from females
Alessandro Moreschi
the last known castrato
removing testes causes behavioural changes
Europe in times past - if you were a young boy with a good voice, the Church might castrate you to keep your voice high (castratos)
childlike voice
first method used to determine if a gland affects a behaviour
ablation and replacement
steps of ablation and replacement
- gland that is suspected to be the source of the hormone affecting behaviour is surgically removed
- effects on behaviour are observed
- hormone is replaced by re-implantation, injection of an extract from the gland, or injecting a purified hormone
- determination is made whether the observed consequences of removal are reversed by the hormonal replacement therapy
Berthold’s experiment
first ever hormones and behaviour experiment
had three groups of chicks
group 1: castrated
group 2: castrated and re-implanted
group 3: castrated and transplanted
Berthold’s experiment: group 1
castrated
caponization
- small comb and wattles
- no interest in hens
- no aggression towards other males
Berthold’s experiment: group 2
castrated and reimplantation of testes
normal male development
- normal comb and wattles
- normal male behaviour
Berthold’s experiment: group 3
castration and transplantation of testes
normal male development
- normal comb and wattles
- normal male behaviour
Berthold’s 3 major conclusions
- testes are transplantable organs
- transplanted testes can function and produce sperm
- because testes functioned normally after all nerves were severed, there are no specific nerves directing testicular function
- so certain glands receive info from innervations, but not all
- can conclude that something in the blood is functioning to affect behaviour
most research in behavioural endocrinology involves only a few types of _______ _______. why?
simple behaviour
this narrow focus on only a few behavioural measures is partially a response to the enormous variation in complex behaviours
this approach has advantages and disadvantages
categorize behaviour into two main classes
- description of action
- how questions: allow us to infer causation and role of experience - description of consequence
- why questions: evolution and function
4 things that flow out of “description of action” and “description of consequence”
mechanisms (how question)
development (how question)
evolution (why question)
function (why question)
2 areas of “how questions”
- immediate causation: the physiological mechanisms underlying behaviour
- development: the role of experience in individual behaviour
2 areas of “why questions”
- evolution: the perspective(s) adopted by biologists who assume that evolutionary processes are central to issues in ecology, systematics, and behaviour
- adaptive function: the role of any structural, physiological, or behavioural process that increases an individual’s fitness to survive and reproduce
3 pieces of evidence needed to determine that a particular hormone affected a specific behaviour OR that a specific behaviour changed hormone concentration
- a hormonally-dependent behaviour should disappear when the source of the hormone is removed, or the actions of the hormone are blocked
- after the behaviour stops, restoration of the missing hormonal source or its hormone should reinstate the absent behaviour
- hormone concentrations and the behaviours in question should be covariant: the behaviour should be observed only when hormone concentrations are relatively high and never/rarely when hormone concentrations are low
latency of action of hormones
have a long latency of action
manner in which many hormones are released (and an example)
pusatile manner
ie. secretion of cortisol occurs approximately every 90 minutes
5 classes of evidence for determining hormone-behaviour interactions
- quasi-experimental designs
- comparison groups
- natural observations
- non-random assignment
- use of statistical controls
quasi-experimental designs
inferring causation in a research setting in cases where experimenting would be unethical/difficult
this approach falls between experimental and non-experimental designs
aims to investigate cause-and-effect like experimental design, but often lacks some key elements (like random assignment)
comparison groups
researchers might compare groups that naturally differ in hormone levels (such as individuals with naturally high vs low testosterone) or groups influenced by external factors (such as individuals using hormone replacemeent therapy versus those not using it)
natural observations
these designs often rely on naturally occurring variations in hormone levels rather than manipulating them artificially
try not to influence/bias the quantification
non-random assignment
participants aren’t randomly assigned to groups due to limitations in controlling or manipulating hormone levels in a controlled manner
instead, researchers observe and compare existing groups
try to account for confounders in the analysis - lack of random assignment makes it harder to establish causality
use of statistical controls
quasi-experimental designs employ statistical techniques to control for confounding variables to strengthen the validity of the findings
lack of random assignment makes it harder to establish…
a clear cause-and-effect relationship between hormones and behaviour
correlational designs
examination of relationships between variables without intervening or manipulating them
instead of seeking causation, they aim to IDENTIFY ASSOCIATIONS/CORRELATIONS between variables to understand how they relate to each other
4 traits of correlational designs
- measurement of variables
- assessment of relationships
- no manipulation of variables
- identification of associations
correlational designs: measurement of variables
researchers measure 2+ variables to determine if they’re related
these variables can be anything measurable (height, age, test scores, hormone levels…)
correlational designs: assessment of relationships
statistical analyses, likely correlation coefficients, are used to assess the STRENGTH and DIRECTION of relationships between variables
correlation coefficients range from -1 to 1 (positive, negative or no relationship)
correlational designs: no manipulation of variables
in contrast to experimental designs, correlational studies don’t manipulate variables or control experimental conditions
instead, they observe and analyze existing data
correlational designs: identifying associations
these studies can reveal is changes in one variable = associated with changes in another variable
ie. correlational study might examine whether there’s a relationship between testosterone levels and aggression
longitudinal designs
study changes in variables over an EXTENDED PERIOD within the SAME INDIVIDUALS/GROUPS
unlike cross-sectional studies that capture data at a single point in time, longitudinal studies follow participants over time
6 key aspects of longitudinal designs
- data collection over time
- tracking changes
- identification of trends and patterns
- analysis of stability and change
- challenges and attrition
- resource-intensive
example of longitudinal study: cortisol in pregnant women
measured cortisol during 1st, 2nd and 3rd trimesters
cortisol release in 1st semester = more similar to non-pregnant women
but in 2nd and 3rd trimester, cortisol is produced more during the day
this expression has an association with depressive symptoms
immunoassays
very important technique in behavioural endocrinology
analytical techniques used for the quantification of an analyte (hormone) based on the antigen-antibody reaction
antigen
a molecule that can bind to a specific antibody
antibodies for a given hormone are produced how?
by injecting the hormone of interest (antigen) into an animal to raise an antibody against the hormone
body produces very specific antibodies, and the given antigen will only bind to a certain antibody
bioassay
assays that use LIVING TISSUES/ANIMALS to test effects of hormones/other chemical compounds
useful historically - measured biological response to hormone in question
sometimes determined PRESENCE/ABSENCE of hormone in question
sometimes allowed QUANTITATIVE MEASUREMENT of specific hormones
test the effects of the hormone and measure its biological activity on a living animal
but require much time and labour
bioassay example: pregnant rabbits
relies on human chorionic gonadotropin (hCG)
^a hormone produced during pregnancy
- take pregnant woman’s urine
- inject that urine into the mice
- if the hCG hormone was present in the mice, the animal’s ovaries would enlarge and show follicular maturation
level of precision in the bioassay rabbit example
98%
bioassays: evolution of pregnancy testing
1927-1960: used the animal testing method (urine injection)
- carried out in lab
1960-1988: antibody testing method (blood tests, pregnancy test sticks)
- carried out at the doctor’s office/at home
radioimmunoassay (RIA) is based on the principle of…
competitive binding of an antibody to its antigen (hormone) that results in a change in radioactivity
a radioactive antigen competes with a non-radioactive antigen for a fixed number of antibody binding sites
an antibody produced in response to any antigen (in this case a hormone) has a binding site that is specific for that antigen
antibodies have a given number of binding sites for its antigen
- antigen molecules can be “labeled” with radioactivity
- antibody cannot discriminate between radiolabeled (hot) and normal (cold) antigen
radiolabeled hormone and cold hormone compete for binding sites on antibody
so the more cold hormone there is present in the tube, the less hot hormone will bind to the antibody
quantity of hot hormone that binds can be determined by precipitating the antibody and measuring the associated radioactivity resulting from the radiolabeled hormone that remains bound
concentration of hormone in sample can then be determined by subjecting sample to same procedure and comparing results with standard curve
competitive binding process in radioimmunoassay
several test tubes with different known concentrations of the hormone (antigens that are unlabeled and radioactive labeled) and the antibody are used to BENCHMARK hormone concentration
cold antigen
in radioimmunoassay, the known hormone concentration
hot antigen
in radioimmunoassay, the known RADIOLABELED hormone concentration
what do radioimmunoassays do?
use antibodies to detect and quantitate the amount of antigen (hormone) in a sample
increase precision with which hormone concentrations can be measured
RIA process
in the well, place antibodies
introduce the corresponding antigen
- labelled antigen
- this will bind to the antibodies
then add the unlabelled antigen (ie. from patient serum)
we want to see if the serum has the unlabelled antigen or not
if the sample has a bunch of unlabeled antigens (radioactive), then radioactivity would DECREASE progressively with the increase in antigen concentration
if the sample has a bunch of unlabeled antigens, then radioactivity…
radioactivity would decrease progressively with the increase of the antigen concentration
if there’s a low level of concentration in the sample, radioactivity…
won’t fall that much
because there’s less competition for binding (less labeled antigens are being replaced by unlabeled antigens)
3 main steps of radioimmunoassay
step 1: immune reaction
- radiolabeled antigen
- competition between labeled and unlabeled antigens
step 2: competitive displacement
- radiolabeled antigen released
- unlabeled antigen (hormone) binds
step 3: radioactivity count
- measure radioactivity
enzyme immunoassay (EIA) or enzyme linked immunosorbent assay (ELISA)
most common way to quantify hormones
uses an enzyme instead of radioactivity
ie. Rapid Covid Test
4 main steps in EIA/ELISA
step 1: have a well of captured antibody
- add the antigen that we want to measure (antigen binds to antibody)
step 2: add labelled antibody
- labelled antibody will attached to first set of antibody/antigen
step 3: add the substrate and enzyme
- substrate will attach to the labelled antibody
- enzyme will cause a change in the substrate that will produce a SIGNAL (ie. change in colour)
detect the signal and/or quantify the product
EIA/ELISA can do what two things…
- detect a hormone (ie. through colour change)
- quantify a hormone using a standard curve (gradient of colour)
immunocytochemistry (ICC) versus immunohystochemistry (IHC)
immunocytochemistry: applied to CELLS
immunohystochemistry: applied to TISSUES
both use antibodies to determine the LOCATION of a hormone in a specific tissue/cell
antibodies linked to marker molecules, such as those in fluorescent dye, are usually introduced into dissected tissue from an animal, where they bind with the hormone/neurochemical of interest
immunofluorescence
use fluorescence to determine the location of a hormone in a specific tissue/cell
what does autoradiography do?
determines the location of hormonal action
(location of hormonal uptake and receptor location)
autoradiography basic idea
radiolabeled hormones are injected into a tissue/animal to determine hormonal uptake and indicate receptor location
4 steps of autoradiography
step 1:
- tissues = sliced into several very thin sections
- adjacent sections = subjected to different treatments
step 2:
- one section of target tissue = stained in usual way to highlight various cellular structures
step 3:
- next section = placed in contact with photographic film
- emission of radiation from radiolabeled hormone develops an image on the film
step 4:
- areas of high radioactivity on the film can then be compared with stained section to see how areas of highest hormone concentration correlate with structures
autoradiography basic process
- determine cellular structures
- use radiation emission to determine location of radiolabeled hormone
- overlay the structure with the hormone locations
(dark spots on photo of structures = where radiolabeled hormone has undergone binding)
blot test - western blot
quantifyies several proteins at the same time
technique used to fractionate mixtures of proteins, DNAs or RNAs so they can hybridize with markers that travel different distances in an electrophorectic gel based on their size
electrophoresis: application of an electric current through a matrix/gel that results in a gradient of molecules separating out along the current basis of size (smaller molecules move farther than larger molecules during a set time period)
steps: blot test - Western blot
step 1: get the sample
- tissue of interest is homogenized and the cells are lysed
- makes it so that all the cells’ contents are loose in the fluid
step 2: homogenate is placed in gel and subjected to electrophoresis
- the small electric current applied to the gel separates the proteins based on their electric charges
step 3: transfer gel to a membrane
- protein bands will have formed
step 4: transfer gel to an incubator with a specific antibody
- antibody is specific to the antigen that is being searched for
step 5: detect bound antibody by chemiluminescence
in blot test/Western blot, how do we detect the bound antibody?
chemiluminescence
can quantify the substrate that emits the colourful reaction
in situ hybridization
determining whether a particular substance is produced in a specific tissue
figuring out WHERE the protein/hormone is produced
in situ hybridization follows the principles of…
immunohystochemistry
technique is used to identify cells/tissues in which messenger RNA (mRNA) molecules encoding a specific protein (hormone/neurotransmitter) are being produced
why does in situ hybridization look for mRNA?
it looks for specific sequences of mRNA - because if that mRNA is present in a tissue it means that gene transcription is happening for the protein of interest
because mRNA is what carries the genetic info needed to produce proteins
4 steps of in situ hybridization
step 1: tissue is fixed, sliced very thin, mounted on slides, and either dipped into an emulsion or placed over film
- developed with photographic chemicals
step 2: tissue is also counterstained to identify specific cellular structures
step 3: radiolabeled cDNA probe is introduced into the tissue. if the mRNA of interest is present in the tissue, the cDNA will form a tight association (hybridize) with it
step 4: the tightly bound cDNA, and hence the mRNA, will appear as dark spots
in situ hybridization: the hybridization part
if the mRNA of interest is present in the tissue, the cDNA will form a tight association (hybridize) with it
hybridization will appear as dark spots
immunohistochemistry versus in situ hybridization
IHC: marks protein
ISH: marks RNA associated with gene expression for the same protein
PCR stands for
polymerase chain reaction
applying immunoassays and genetic marking for COVID - PCRs
PCRs use fluorescence
PCRs amplify and replicate a specific segment of DNA and RNA
this process creates NUMEROUS copies of the targeted DNA/RNA
this enables detection and analysis
basically, saliva provides nucleic acids and RNA or DNA - any viral contents will be marked and become fluorescent
the viral mRNA will bind to complementary DNA of the test
then we’ll create a reaction to amplify the signal and we can quantify the presence of the hormone
applying immunoassays and genetic marking for COVID - lateral flow immunoassay technology
in a RAPID ANTIGEN TEST
patient test sample is mixed with chemicals that react with specific proteins on the surface of the SARS-Cov-2 virus
saliva swabs - if mRNA from virus is present, the immune response will occur and colour will change
7 types of immunoassays
- bioassays
- radioimmunoassays
- enzyme immunoassays (EIA) or enzyme linked immunosorbent assay (ELISA)
- autoradiography
- blot tests
- in situ hybridization
bioassay in a nutshell
biological assays assessing the effects of substances
uses living animal tissues
radioummunoassay in a nutshell
measures concentrations of antigens using radioactive labels
concentrations of a given hormone is inversely related to the radioactive labels
measures concentrations using standard curves
enzyme immunoassay (EIA) or enzyme linked immunosorbent assay (ELISA)
detects antigens or antibodies using enzyme-based reactions
immunocytochemistry (ICC)/immunohystochemistry
visualizes proteins in cells (ICC) or tissues (IHC)
does this using immmunohystochemistry
labels antibodies with dyes or enzymes
autoradiography in a nutshell
captures and visualizes radioactively labeled molecules in the tissue
photographic film is overlayed with an adjacent stained tissue
blot wests in a nutshell
techniques (ie. Western blot) for transferring and detecting biomolecules using specific probes
detects several proteins at same time
in situ hybridization in a nutshell
locates and visualizes specific nucleic acid sequences (ie. mRNA) within cells or tissues
pharmacological techniques
use of synthetic chemical agents can alter the action/function of a hormone
two major groups of synthetic chemical agents
2 major groups of synthetic chemical agents
- agonists: simulate endocrine function by affecting hormonal release
- antagonists: inhibit endocrine function by affecting hormonal release (blocking hormones)
example of pharmacological technique
cyproterone acetate -> anti testosterone
cyproterone acetate binds to the testosterone reception
inactivates it
testosterone levels fall
brain imaging 2 techniques
- Positron Emission Tomography (PET)
- Functional Magnetic Resonance Imaging (fMRI)
positron emission tomography
PET
injection of radiotracers - specific molecules (hormone)
PET scanner detects the radioactivity as the compound accumulates in different regions
can infer the locus of the hormone’s action
functional magnetic resonance imaging
fMRI
involves exposing brain to multiple magnetic fields
high spatial and temporal resolution
detects changes in brain activity during specific tasks/conditions
can be task-based or resting-state
gene
discrete region of DNA within a chromosome that when expressed (transcribed), leads to the production of ribonucleic acid (RNA)
transgenic
relating to an animal in which a gene has been INSERTED, ALTERED, or DELETED
knockout
an individual, usually a mouse, in which a specific gene has been INACTIVATED
chimera
animal whose tissues are composed of two or more genetically distinct cell types
alter DNA in the embryonic (not yet differentiated) cells
- these cells will multiply in the embryo
- born as chimera
alternative name for a chimera
mosaic
new inducible knockouts
new innovation
timing and tissue-specific placement of the targeted gene disruption can be controlled
genetic manipulations
insertion, alteration (over or under-expression), deletion of genes
study resulting behaviour
CRISPR/Cas 9
CRISPR (clustered regularly interspaced short palindromic repeats)
revolutionary tech in molecular biology that allows precise editing of genes WITHIN organisms
involves cutting DNA at specific location using the Cas9 protein guided by a designed RNA sequence
this precise DNA cleavage allows researchers to introduce modifications by relying on the cell’s natural repair mechanisms
allows insertion of new DNA sequence
integrating diff hormone & behaviour methods: hunger hormones - Leptin
leptin is a hormone that helps maintenance of normal weight on a long term basis
level of leptin in blood is directly related to…
the amount of body fat that you have
leptin resistance causes you to…
feel hungry and eat more even though your body has sufficient fat stores
ob mice
specific mutations in mice cause extreme obesity in those that are homozygous for the defective gene
considered natural knockouts
from the ob mice, a mice strain was devised for…
studies of body mass regulation
ob/ob mice have a pair of…
defective ob genes
they are HYPERPHAGIC (overeat), obese, reproductively sterile
researchers take advantage of purified leptin…
availability of purified leptin allows researchers to produce specific antibodies to this substance that could be used in developing assays to determine concentration in blood
an RIA was developed to…
determine the blood plasma leptin concentrations of obese and diabetic humans
the anti-leptin antiserum was raised in a rabbit against highly purified recombinant human leptin
immunocytochemical localization techniques revealed that leptin was present in…
both white and brown adipose tissue as well as other peripheral tissues
to determine the site of action of leptin in the brain…
purified leptin was labeled with a radioactive tag and then injected into mice
autoradiography
differences in what blot tests versus in situ hybridization can determine
blot tests can typically determine WHETHER OR NOT a particular substance is PRESENT in a specific tissue
in situ hybridization can determine WHETHER a particular substance is PRODUCED in a specific tissue
- can also quantify the substance being produce
- and have higher resolution/sensitivity than blot tests
hormones
chemical messengers that travel through the blood stream
target specific organs/tissues
hormones coordinate…
the physiology and behaviour of an animal
they do this by regulating, integrating and controlling its bodily function
can hormones have more than one effect?
yes
examples: gonadotropin hormone, epinephrine
can hormonal messages travel anywhere in the body?
yes
they can travel anywhere in the body via the circulatory system
any cell receiving blood is potentially able to receive a hormonal message
hormonal messages can travel up to 2 meters in the blood system
main 2 differences between hormonal and neural signalling
- speed
- because hormones travel through the blood, hormonal signals are slower than neural ones - precision
- as hormones travel long distances, they need very specific receptors
- the specificity of receptors is what makes hormonal signalling so precise
double action of the epinephrine hormone
epinephrine can have more than one effect
- in liver cell
- epinephrine binds to beta receptor
- causes glycogen deposits to break down
- glucose is released from cell - in skeletal muscle blood vessel
- epinephrine attaches to beta receptor
- vessel dilates
5 forms of chemical communication
- intracrine mediation
- autocrine mediation
- paracrine mediation
- endocrine mediation
- ectocrine mediation
intracrine mediation
intracrine substances regulate INTRACELLULAR events
ie. molecules produced at the nucleus of a neuron affect the axon of the same cell
autocrine mediation
autocrine substances feed back to influence the same cells that secreted them
LEAVE AND THEN RETURN TO THE SAME CELL
affect the cell that first produced the hormone
cells have receptors for their own products
paracrine mediation
paracrine cells secrete chemicals that affect ADJACENT CELLS
endocrine mediation
endocrine cells secrete chemicals into the BLOODSTREAM, where they may travel to DISTANT TARGET CELLS
ectocrine mediation
released into the ENVIRONMENT by individuals to communicate with others
ie. pheromones
chemical messenger
any substance that is produced by a cell that affects the function of another cell
cytokine
chemical messenger that evokes proliferation of other cells
especially in the immune system
hormone
chemical messenger that’s released into the bloodstream or tissue fluid system that affects the function of target cells some distance from the source
neurohormone
hormone produced by a neuron
neuromodulator
hormone that changes (modulates) the response of a neuron to some other factors
neuropeptide
peptide hormone produced by a neuron
neurosteroid
steroid hormone produced by a neuron
neurotransmitter
chemical messenger that acts across the neural space
can neurotransmitters be neurohormones?
yes
produced in hypothalamus or pituitary
pass along the axons of neurons and then are released into the bloodstream
examples of neurohormones
oxytocin
vasopressin
norepinephrine
gonadotropin-releasing hormone
corticotropin-releasing hormone
T/F: endocrine glands are ductless
true
closed structure - no ducts that communicate with body
so rely on blood vessels for communication
T/F: endocrine glands have a rich blood supply
true
5 main features of the endocrine system
- endocrine glands are ductless
- endocrine glands have a rich blood supply
- hormones, the products of endocrine glands, are secreted into the bloodstream
- hormones can travel in the blood to virtually every cell in the body and can thus potentially interact with any cell that has appropriate receptors
- hormone receptors are specific binding sites, embedded in the cell membrane or located elsewhere in the cell, that interact with a particular hormone/class of hormones
where are hormone binding sites/receptors located?
either embedded in the cell membrane
or located elsewhere in the cell
can glands be both endocrine and exocrine?
yes
like the pancreas
endocrine versus exocrine
exocrine:
- secrete substances into a ductal system to an epithelial surface
endocrine:
- secrete products directly into the bloodstream
pancreas: endocrine and exocrine components
exocrine: pancreas secretes digestive juices into the intestines via DUCTS
endocrine: pancreas secretes hormones directly into the BLOODSTREAM
from here they travel throughout the body to regulate energy utilization and storage
receptor concentration and hormone concentration can interact…
insufficient receptors might cause endocrine deficiency
if there aren’t enough receptors, we call this ‘resistance’
ie. insulin resistance
cross-reaction
when the blood concentration of a hormone is high, they can sometimes bind with receptors that are meant for a different hormone
causes a biological response
hormone molecules vary substantially in…
- size
- chemical properties
major chemical classes of hormones
polypeptides (proteins and peptides)
steroids
amines
lipid-based (some authors don’t include this last one)
amines can be both…
water-soluble (hydrophilic)
or
lipid-soluble (hydrophobic)
other term for water-soluble
hydrophilic
other term for lipid-soluble
hydrophobic
polypeptides: hydrophilic or hydrophobic?
hydrophilic (water-soluble)
so they dissolve well in watery plasma blood
but the cell membrane = lipid - so water can’t mix
so polypeptides bind to the cell’s surface receptors, which relay info to nucleus via intracellular signalling
where are polypeptides stored?
in vesicles within cells
can’t freely enter cell because cell membrane is made of lipids
steroids: hydrophilic or hydrophobic?
hydrophobic (lipid-soluble)
can easily pass through the lipid cell membrane
but cannot travel through watery blood
so need a transporter protein to move through blood
to travel through blood, what to steroids need?
a transporter protein
because steroids are hydrophobic
how are peptide hormones released from parent cell? how about steroid hormones?
peptide hormones = exocytosis
steroid hormones = simple diffusion
reminder: study hormone chart
it’s in onenote
if a hormone acts inside a nucleus, it likely has…
transcriptional properties
any hormone with ‘chorionic’ in its name is…
produced by the placenta
8 major endocrine structures
- hypothalamus
- pineal gland
- pituitary gland (anterior and posterior)
- thyroid
- adrenal glands (medulla and cortex)
- pancreas
- gut
- gonads (testes/ovaries)
hypothalamus: main function it regulates
control of hormone secretions
pineal gland: main function it regulates
reproductive maturation
body rhythm
anterior pituitary: main function it regulates
hormone secretion by thyroid, adrenal cortex and gonads
growth
posterior pituitary: main function it regulates
water balance
salt balance
thyroid: main function it regulates
growth and development
metabolic rate
adrenal cortex (outer bark): main function it regulates
salt and carbohydrate metabolism
inflammatory reactions
adrenal medulla (inner core): main function it regulates
emotional arousal
pancreas (islets of Langerhans): main function it regulates
sugar metabolism
gut: main function it regulates
digestion and appetite control
gonads (testes/ovaries): main function it regulates
body development
maintenance of reproductive organs in adults
hypothalamus
comprises several collections of neuronal cell bodies (nuclei)
at the base of the brain
receives projections from the brain
controls hormone secretion (and produces hormones)
2 main types of hormones released by the hypothalamus
- releasing hormones
- stimulates the release of certain hormones from glands - inhibiting hormones
- inhibits the release of certain hormones from glands
hypothalamus: 6 main releasing hormones
- thyrotropin-releasing hormone (TRH)
- growth hormone-releasing hormone (GHRH, somatocrinin)
- gonadotropin-releasing hormone (GnRH)
- melanotropin-releasing hormone (MRH)
- corticotropin-releasing hormone (CRH)
- kisspeptin
^these are all EXCITATORY
hypothalamus: 3 main inhibiting hormones
- somatostatin (growth hormone-inhibiting hormone/GHIH)
- gonadotropin inhibitory hormone (GnIH)
- dopamine (DA)
^these are all INHIBITORY
where is the hypothalamus and what is it composed of?
it’s at the base of the brain
comprises several collections of neuronal cell bodies or nuclei
receives projections from the brain
corticotropin-releasing hormone (CRH)
excitatory hypothalamic hormone
stimulates secretion of ADRENOCORTICOTROPIC hormone
releasing hormones do what
act on another gland - get it to release a hormone
every time you see ‘tropic’, think about…
nourishment
ie. adrenocorticotropic means a hormone that nourishes the adrenal gland
gonadotropin-releasing hormone (GnRH)
excitatory hypothalamic hormone
controls the release of:
- LUTEINISING HORMONE (LH)
- FOLLICLE-STIMULATING HORMONE (FSH)
growth hormone-releasing hormone (GH-RH)
excitatory hypothalamic hormone
tells appropriate gland to release growth hormone (GH)
thyrotropin-releasing hormone (TRH)
excitatory hypothalamic hormone
tells pituitary gland to produce/release THYROID-STIMULATING HORMONE (TSH)
melanotropin releasing hormone (MRH)
excitatory hypothalamic hormone
stimulates secretion of melanotropin
kisspeptin
excitatory hypothalamic hormone
initiates secretion of gonadotropin-releasing hormone (GnRH) at puberty
thus is involved in sexual maturation
but it role isn’t yet clearly described
dopamine (DA)
inhibitory hypothalamic hormone
dopamine is typically excitatory but in the endocrine system it’s inhibitory
prolactin-inhibitory hormone
somatostatin (SOM)
inhibitory hypothalamic hormone
acts to inhibit secretion of:
1. growth hormone (GH)
2. thyroid-stimulating hormone (TSH)
also has inhibitory effects on insulin, glucagon, secretin production
pituitary gland was once considered what?
the “master gland”
why was pituitary once considered the “master gland”?
because it mediates so many physiological processes - it secretes many hormones
but now we know that it receives lots of commands from the hypothalamus
it’s really two distinct glands fused into one
the two different embryological origins of the pituitary
- roof of the mouth = anterior pituitary
- base of the brain = posterior pituitary
how do neurohormones from hypothalamus reach anterior pituitary?
via the PORTAL SYSTEM
portal system
the way that neurohormones travel from the hypothalamus to the anterior pituitary
special closed blood circuit
two beds of capillaries (one in hypothalamus and one in anterior pituitary) are connected by a vein
hypothalamic factors stimulate cells in the anterior pituitary to secrete hormones in general circulation
how do neurohormones from hypothalamus reach posterior pituitary?
hypothalamic neuro-secretory cells
these cells innervate DIRECTLY to the posterior pituitary
rather than being released into portal system, neurohormones are secreted directly into this structure
here they enter blood vessels and the general circulation
anterior pituitary: 3 steps of hormone release
- axon terminals of hypothalamic neurons release neurohormones near capillaries that give rise to portal vessels
- neurohormones from portal vessels stimulate or inhibit the release of hormones from anterior pituitary cells
- anterior pituitary hormones leave the gland via the blood
so two steps really: hypothalamus releases neurohormones into the portal and then in response, the pituitary releases the specific hormones into general circulation
3 main anterior pituitary hormones
- corticotropin-related peptides (painkillers/stress response)
- adrenocorticotropic hormone (ACTH)
- melanocyte-stimulating hormone
- beta-endorphins - somatomammotropins (growth, breast milk)
- growth hormone (GH or somatotropin)
- prolactic (PRL) - glycoproteins (thyroid, gonads, sex hormones)
- thryoid-stimulating hormone (TSH)
- luteinizing hormone (LH)
- follicle-stimulating hormone (FSH)
what do corticotropin-related peptides do?
(anterior pituitary hormones)
- ACTH:
stimulate synthesis/release of the following from the adrenal glands:
- glucocorticoids
- mineralocorticoids
- androgenic steroids
- exposure to stressful events can trigger ACTH release
- beta-endorphins:
endogenous opioids that resemble opiates in its action as a “natural” pain killer
anterior pituitary hormones are often considered as what? and why?
polypeptides tropic hormones
because they stimulate various physiological processes
either by acting directly on target tissues or by causing other endocrine glands to release hormones
what do somatomammotropins do?
(anterior pituitary hormones)
(think ‘soma’ - ‘body’ - growth)
- growth hormone (GH):
promote linear growth
a) GH and somatotropin:
enhance amino acid uptake and mRNA transcription/translation
- increased protein synthesis
- prolactin:
promotes breast development, initiates milk synthesis
what do glycoproteins do?
(anterior pituitary hormones)
- TSH:
works on thyroid gland to stimulate uptake of iodide and release of thyroid hormones - LH and FSH:
bind to receptors in ovaries and testes, regulate gonad function
stimulate sex steroid production and development of gametes
posterior pituitary: 3 steps of hormone release
- hypothalamic neurons produce vasopressin and oxytocin and transport them to the posterior pituitary
- the neurohormones are released in the posterior pituitary and diffuse into capillaries
- then leave the posterior pituitary via the blood
hormones from posterior pituitary enter circulation more quickly than those from anterior pituitary
oxytocin and vasopressin in relation to the posterior pituitary
- oxytocin and vasopressin = made and packaged in neurosecretory cell bodies
- then are transported down the axons to be stored in vesicles at the axon terminals in the posterior pituitary
- can be released in response to a NEURAL IMPULSE via exocytosis and enter the bloodstream
SO POSTERIOR PITUITARY HORMONES CAN BE RELEASED AS FAST AS NEURAL IMPULSES
how are vasopressin and oxytocin released?
FROM VESICLES, SUPER QUICKLY
released from vesicles at axon terminals
in response to neural impulse via exocytosis
from here enter bloodstream
release is as fast as neural impulses
hormones associated with the posterior pituitary
vasopressin
oxytocin
vasopressin
aka antidiuretic hormone (ADH)
acts to retain water in the body
what does vasopressin do during serious blood loss?
it has pressor (hypertensive) effects
pressor - pressin
it causes the CONSTRICTION of blood vessels to help deal with blood loss
oxytocin (5 points)
- influences reproductive function in mammals
- important during birth
- causes uterine contractions
- often used to medically induce labour
- involved in suckling reflex
reminder to look at screenshot of hypothalamic hormones and what hormones they stimulate/inhibit
it’s on desktop
pineal gland location
top of midbrain
above third ventricle
just in front of cerebellum
pineal gland secretes what?
melatonin
what pineal cells produce melatonin?
secretary cells called PINEALOCYTES
produce melatonin, that resembles serotonin
pinealocytes
cells in the pineal gland
they produce melatonin
how is melatonin synthesized?
synthesized from melatonin via the amino acid tryptophan
how is melatonin secreted?
secreted into cerebrospinal fluid and bloodstream
what is melatonin secretion regulated by?
the sympathetic NS in response to changing light levels
as light levels fall, melatonin secretion increases
as light levels rise, melatonin secretion ceases
pineal gland’s main function
related to control of the CIRCADIAN CYCLE OF SLEEP AND WAKEFULNESS by secreting melatonin
thyroid
large bilateral structure
in the neck
consists of many spherical follicles
what do the thyroid’s spherical follicles produce?
thyroid hormones
in direct response to the thyrotropin-releasing hormone released by the anterior pituitary
what does the thyroid gland produce?
iodinated substances
T3 and T4
produces these dependent upon dietary levels of iodate
low levels of dietary iodine result in REDUCED THYROID FUNCTION and HYPERTROPHY
how does reduced thyroid function and hypertrophy manifest physiologically?
swelling in the neck
thyroid hormones do what?
increase oxidation rates in tissue
3 general areas of effect in mammals:
1. metabolism
2. growth and differentiation
3. reproduction
2 thyroid hormones
triiodothyronine (T3)
thyroxine (T4)
both T3 and T4 are fat-soluble, and they diffuse…
rapidly across cell membranes
but they need carrier protein to travel through the blood
4 key functions of T3 and T4
- regulation of body metabolism
- control of development of brain and nervous system
- sexual maturation
- temperature regulation
2 forms of thyroid dysfunction
- hyperthyroidism
- too much T3 and T4 are produced
- weight loss, fast heart rate, weak menstrual cycle, shaky hands - hypothyroidism
- under-active thyroid
- weight gain, constipation, cold sensitivity
Ronaldo was diagnosed with what?
hypothyroidism
had problems with weight
parathyroid glands are located where?
at the rear of the thyroid
hormones produced by the parathyroid gland and by C cells of the thyroid are both…
- both are protein hormones
- both are involved in calcium metabolism
parathyroid (PTH)
produced by C cells
elevates blood levels of calcium
does this by increasing reabsorption of calcium from the bone and from the gut
via its effects on vitamin D3
also inhibits phosphate reabsorption from the kidney, reducing calcium clearance
calcitonin (CT)
released from C cells of the thyroid
acts in opposition to parathyroid hormone
lowers blood levels of calcium by inhibiting the release of calcium from bone
PTH and CT are both controlled directly by…
blood calcium levels
there are no pituitary tropic hormones (releasing hormones) involved in their regulation
direct reaction to calcium levels in blood
pancreas functions as both…
an endocrine and exocrine gland
most of the pancreas consists of…but…
exocrine cells
these produce and secrete DIGESTIVE JUICES into the intestines
BUT nested throughout the exocrine tissue are islands of endocrine tissue called islets of Langerhans
exocrine cells of pancreas do what?
produce and secrete digestive juices into the intestines
what are the endocrine cells of the pancreas called?
islets of Langerhans
islets of Langerhans
islands of endocrine tissue nested throughout the exocrine tissue of the pancreas
within these endocrine islands, there are 4 cell types:
- alpha cells
- beta cells
- theta cells
- polypeptide-secreting cells
glucagon
simple peptide
similar to those of secretin family
typically has 29 amino acids
released from alpha cells of the pancreas
do all cells have insulin receptors?
yes, all cells do
NS (neuronal) cells do as well
so insulin can have effects in the CNS as well as the PNS
insulin resistance is correlated with depression and bipolar
where does glucagon go once released from alpha cells?
once released from the alpha cells of the pancreas, glucagon travels first to the liver
in the liver it stimulates glycogenolysis
glycogenolysis
breakdown of stored glycogen
this acts in opposition of insulin and serves to increase blood levels of glucose
alpha cells do what? for what purpose?
alpha cells release gulcagon
glucagon travels to the liver
there it stimulates glycogenolysis (breakdown of stored glycogen)
acts in opposition of insulin: SERVES TO INCREASE BLOOD LEVELS OF GLUCOSE
ultimately, alpha cells do what?
release glucagon to increase blood levels of glucose
beta cells produce what?
insulin
what does insulin promote?
efficient movement of energy from the blood into the cells
can lower blood sugar
diabetes
disease caused by:
- insulin deficiency
- decreased response to insulin in target tissues
thought that in type I diabetes, pancreatic islets are destroyed by immune assaults (autoimmune disorder)
insulin is the only known hormone that can…
lower blood sugar
glucagon versus insulin
- glucagon releases glucose into blood stream
- insulin lowers blood sugar
they work in opposition with one another
theta cells
release somatostatin
somatostatin inhibits insulin release and glucagons locally in the pancreas
somatostatin
inhibitory hormone released from theta cells
inhibits insulin and glucagon release in pancreas
somatostatin = also released from hypothalamus to regulate release of growth hormone from anterior pituitary
type I versus type II diabetes
type I:
- genetic condition appearing in early life
- auto-immune condition: immune system attacks and destroys insulin-producing beta cells in the pancreas
type II:
- lifestyle related disease
- develops over time
- either your body isn’t able to produce sufficient insulin because you’re consuming too much sugar OR the insulin you create isn’t working properly
type III?
- alteration of insulin metabolism in brain
- common in Alzheimer’s
two possibilities in type II diabetes
- body can’t produce enough insulin because you’re consuming too much sugar
- the insulin being produced by your body isn’t working properly
adrenal gland location
atop the kidneys
2 distinct regions of the adrenal gland
- adrenal cortex
- adrenal medulla
adrenal cortex
has distinct cellular zones with diff functional roles
- zona glomerulosa (outside)
- zona fasciculata (middle)
- zona reticularis (inside)
zona glomerulosa
marked by WHORLS of epithelial cells
aldosterone
zona fasciculata
epithelial cells are organized in ORDERLY BANDS
glucocorticoid
zona reticularis
epithelial cells are DISORGANIZED
sex steroid hormones
adrenal medulla
made up of CHROMAFFIN CELLS
in embryonic development: these cells = derived from primitive neural tissue
after birth they work as part of the ANS
respond to neural signals
chromaffin cells
make up the adrenal medulla
derived from embryonic primitive neural tissue
post-birth: work as part of ANS
respond to neural signals that come from the spinal cord
in response to neural signals, adrenal medulla releases…
3 monoamine hormones
3 monoamine hormones released by the adrenal medulla
- epinephrine
- norepinephrine
- dopamine
class of protein hormones released from adrenal medulla (in addition to the monoamine hormones)
enkephalins
why/how is the adrenal medulla important for fight or flight?
epinephrine and norepinephrine
and because chromaffin tissue: receives neural signals so quite fast
HPA axis
hypothalamic pituitary adrenal axis
tissue in medulla of adrenal glands receives info through what?
through innervations to spinal cord
short term effects - fast
tissue in adrenal cortex receives info through what?
the blood
longer term effects - more prolonged
3 zones of the adrenal cortex release what hormones?
- aldosterone
- glucocorticoid
- sex steroid hormones
2 functions of gonads
(these functions are usually compartmentalized)
- production of GAMETES (sperm or eggs)
- production of HORMONES
hormones produced by gonads are primarily of what type?
steroid hormones
what are steroid hormones required for?
gamete development
development of secondary sex characteristics
also mediate behaviours necessary to bring sperm and eggs together
what regulates the function of the gonads?
tropic hormones from the anterior pituitary
these are called gonadotropins
gonadotropins
tropic hormones from the anterior pituitary
regulate gonad function
HPG axis
hypothalamic pituitary gonad axis
testes
bilateral glands
located in most mammals in an external sac called the scrotum
seminiferous tubules
seminiferous tubules
long, convoluted tubes
where sperm cells undergo various stages of maturation (spermatogenesis)
sertoli cells
located along basement membrane of seminiferous tubules
involved in spermatogenesis
facilitate progression of germ cells to spermatozoa
via direct contact and by controlling environmental milieu within seminiferous tubules
leydig cells
interstitial cells between seminiferous tubules in the testes
produce androgens/testosterone
leydig cells produce testosterone in response to what?
in response to the luteinizing hormone from the anterior pituitary
sertoli versus leydig cells
both work in testes
sertoli: aid spermatogenesis
leydig: produce androgens in response to LH
ovaries: 4 main features
- paired glands located in dorsal part of abdominal cavity, normally below kidneys
- compartmentalized (diff parts have diff functions)
- within fetal ovary are germinal epithelia - eventually develop into primordial follicles
- infant ovaries contain about 500 000 immature follicles
- approx 400 eggs (ova) are ovulated by women between puberty and menopause - three functional units:
- follicles
- corpora lutea
- stroma
where are the ovaries located?
dorsal part of the abdominal cavity
normally below the kidneys
ovaries: germinal epithelia eventually develop into…
primordial follicles
how many immature follicles are contained in infant ovaries?
about 500 000
how many eggs are ovulated by average woman between puberty and menopause?
400 eggs
3 main functional subunits of the ovaries
- follicles
- corpora lutea
- stroma
atresia
the continual degeneration of follicles throughout life
no additional gametes are formed postnatally
stroma
noendocrine connective tissue of endocrine glands
follicles
epithelial cell-lined sacs that contain an egg
egg/ovum
haploid female gamete
contained in folliclees
corpora lutea
endocrine structures that form from remnants of ovarian follicles after the egg is released
secrete progestins
what secretes progestins?
corpora lutea
what do progestins do?
support the uterine lining in prep for blastocyst implantation
each primary follicle consists of an…
ovocyte
ovocyte
an immature egg
what surrounds the ovocyte?
layer of epithelial cells called GRANULOSA cells
granulosa cells
epithelial cells that surround the ovocyte
what do granulosa cells produce? what do these cells regulate?
two peptide hormones
- inhibin
- activin
these hormones regulate hypothalamus and pituitary gland
theca cells
surround granulosa cells
during follicular maturation
these cells participate in estrogen synthesis
antrum
space between ovum and surrounding epithelial cells
filled with fluid prior to ovulation
as the antrum enlarges, the follicle is called a…
tertiary follicle
antrum fluid
called the follicular fluid
is rich in steroid hormones
what is in follicle called when it reaches its maximal size?
Graafian follicle
what happens to the granulosa cells and theca cells after ovum release?
after ovum release
both granulosa cells of the erupted follicle
and the surrounding thecal cells
UNDERGO RAPID MITOSIS
and CAPILLARIES GENERATED FROM THE THECAL CELLS VASCULARIZE THE GRANULOSA CELLS
how does the corpus luteum form?
from the rapid mitosis that occurs in the granulosa and thecal cells following ovum release
and from the vascularization of the granulosa cells by the capillaries generated from the thecal cells
how long does the corpus luteum persist for? what do they do?
corpus luteum persists for some time on surface of ovary
produce another class of important sex steroid hormones: progestins
progestins
important sex steroid hormones
produced by the corpus luteum after ovum release
zona pellucida
multiple layer of epithelial cells that surrounds the follicle
placenta: 4 main features
- temporary endocrine organ that develops in uterus during mammal pregnancy
- forms from tissues derived from blastocyst and maternal uterus - important in maintaining nutritional, respiratory, and excretory functions for fetus
- source of several steroid and peptide hormones that affect mother and offspring
- pregnancy tests measure human chorionic gonadotropin (hCG), a hormone produced by rudimentary placenta that forms right after blastocyst implantation
what does the placenta form from?
tissues derived from:
- blastocyst
- maternal uterus
what functions is the placenta important for maintaining within the fetus?
- nutritional functions
- respiratory functions
- excretory functions
placenta is the source of several _____ and ______ _____ that affect both the _____ and the _______
steroid and peptide hormones
mother and the offspring
what do pregnancy tests measure?
human chorionic gonadotropin (hCG)
^hormone produced by rudimentary placenta that forms immediately after blastocyst implantation
blastocyst
cluster of dividing cells made by a fertilized egg
early stage of the embryo
what’s relaxin produced by?
not produced by placenta
BUT by the corpora lutea during pregnancy
what does relaxin do?
softens the estrogen-primed PELVIC LIGAMENTS
to allow enough stretch for the passage of large head of fetus through the pelvis
“supplementary” tropic hormones released by the placenta do what?
stimulate the:
- gonadal
- mammary
- adrenal
- thyroid
functions
what are the 4 supplementary protein hormones released by the placenta?
- chorionic gonadotropins (CG)
- chorionic somatomammotrophin (CS, aka palcental lactogen)
- chorionic corticotropin (CC)
- chorionic thyrotropin (CT)
chorionic gonadotropin
hCG
- maintains corpora luteal function (and progesterone secretion) during pregnancy
- part of regulatory system that inhibits ovulation during pregnancy
if chorionic is in the name…
then it’s produced in the placenta
what hormone helps inhibit ovulation during pregnancy
chorionic gonadotropin
hCG
gastrointestinal hormones: 3 main features
- endocrine cells of gastrointestinal tract = scattered throughout gut
- in a “primitive organization” - gastrointestinal hormones regulate cells and organs in which they’re produced
- intracrine/autocrine chemical mediation is usually considered a more primitive mechanism that endocrine mediation - main hormones: secretin, cholecystokinin, ghrelin
- these hormones = released into circulation and act to supplement the actions of the ANS during digestion
endocrine cells of gastrointestinal tract are organized in what fashion?
scattered around the gut
in what is called a PRIMITIVE ORGANIZATION
what kind of chemical mediation occurs for gastrointestinal hormones?
intracrine/autocrine chemical mediation
these hormones regulate the cells and organs in which they are produced
secretin
small peptide of 27 amino acids
release of secretin by duodenal mucosa = stimulated by passage of food into small intestine
stimulates pancreas to produce secretions which aid in digestion
what releases secretin? what stimulates it?
duodenal mucosa
release is stimulated by passage of food into small intestine
what does secretin do?
it stimulates the pancreas to produce secretions which aid in digestion
- stimulation of hepatic (liver) tissue
- pepsin secretion
- inhibition of gastrointestinal (GI) tract movement and gastric acid secretion
cholecystokinin (CKK)
hormone released by lining of small intestine that may be involved in satiation of food intake
causes exocrine pancreas to secrete digestive enzymes
CKK also causes gallbladder to contract/release bile
what releases cholecystokinin (CKK)?
lining of the small intestine
CKK causes exocrine pancreas to do what?
secrete digestive enzymes
CKK causes gallbladder to do what?
contract/release bile
CCK hormone has been identified where outside of the gastrointestinal tract?
in the brain
here it functions as a neurotransmitter or nueromodulator
gastrin
peptide hormone
secreted by mucous layer of stomach
induces secretion of water and electrolytes by stomach, pancreas, liver
induces secretion of enzymes by stomach and pancreas
produced in antral glands of stomach
gastrin is secreted by…
mucous layer of the stomach
what does gastrin do?
induces secretion of:
- water and electrolytes by the stomach, pancreas and liver
- enzymes by the stomach and pancreas
where is gastrin produced?
antral glands of the stomach
what does ghrelin do?
stimulate GHRH from anterior pituitary
where is ghrelin made?
endocrine cells in the stomach
what happened when ghrelin was administered to mice?
was done to see if it would enhance GH secretion
food intake and fat deposition increased
human participants treated with ghrelin…
ate about 30% more food than individuals not given the hormone
concentrations of ghrelin increased to peak levels prior to each meal (~80% increase) and fell dramatically after the meal
2 basic patterns of internal hormonal regulation
- regulation by the physiological by-products generated in response to their actions (thermostat)
- regulation by the stimulatory or inhibitory effects of other hormones
example of regulation of hormones by the physiological by-products generated in response to their actions
ie. parathyroid hormone is released when blood levels of calcium decrease
when the action of the hormone has raised concentration of blood calcium to an optimal level, parathyroid hormone secretion stops
thermostat analogy
example of hormonal regulation by the stimulatory or inhibitory effects of other hormones
within this form of control, one or more hormones in a regulatory chain may be involved in hormonal regulation
ie. GnRH is regulated by a multiple chain of negative feedback
negative feedback
part of hormonal regulation
a regulatory system that tends to STABILIZE a process when its effects are pronounced by REDUCING ITS RATE/OUTPUT
positive feedback
part of hormonal regulation
a regulatory process that tends to ACCELERATE an ongoing process by INCREASING PRODUCTION in response to the end product
generally less frequent - must be tightly controlled
ie. short term stress response can’t be let go on for too long
can hormones affect the levels of their own receptors?
yes
through up-regulation or down-regulation
up-regulation
process similar to positive feedback
hormone causes INCREASE in production of RECEPTORS for that hormone
down-regulation
overproduction of a hormone can cause occupation or REDUCE the number of hormone RECEPTORS
cellular and molecular mechanisms of hormone action
hormonal messages/signals evoke intracellular responses via SIGNAL TRANSDUCTION
essentially, the chemical hormonal message is transformed into intracellular events that ultimately affect cell function
signal transduction
the way in which hormonal messages/signals evoke intracellular responses
signal transduction pathway
sequence of events that begins with a hormone binding to its receptor and ends with the ultimate response in a target cell
steroid hormone receptors: signal transduction
steroid hormone receptors = located inside cells (cytosol or nucleus)
steroids = lipid soluble, so can penetrate cell membrane to bind with these intracellular receptors
when the receptors bind to a specific steroid/thyroid hormone, they migrate to nucleus
here, they regulate gene transcription
protein and peptide hormone receptors: signal transduction
protein/peptide hormone receptors = embedded in cell membrane
have at least three domains with specific functions
- extracellular domain (binds to hormone to form hormone-receptor complex)
- transmembrane domain
- cytoplasmic/intra-cellular domain (inside cells, often transmits a signal)
protein/peptide hormones have two types of activity…
- intrinsic enzymatic activity
- have enzymes in the cytoplasmic domain that phosphorylate/activate intracellular proteins - require a second messenger
- these receptors are coupled to G proteins
- G proteins are activated when the appropriate hormone binds to the receptor
- this part of the activated G protein activates an effector protein that converts thousands of reactants to products, amplifying action within the cell
what is the definition of sex?
several ways to answer this
because there are different levels of sexual determination
each step of mammalian sexual development = a different step in a cascade of events
why do sex differences exist?
some species don’t have different sexes: they reproduce asexually
ie. white spotted bamboo shark
but asexual reproduction results in less genetic diversity
so, SEXUAL REPRODUCTION PROVIDES GENETIC VARIABILITY THAT ENHANCES EVOLUTIONARY FLEXIBILITY
through the separation of haploid pairs in parents and their recombination in offspring
combo of genetic info = more flexibility
why do sexually dimorphic behaviours exist?
mating system
either MONOGAMOUS or POLYGAMOUS
sex differences = reduced in monogamous species
ie. prairie voles are monogamous: virtually impossible to tell male and females apart
ie. elk are polygamous: males and females are readily distinguishable
what kind of mating system causes more sexually dimorphism?
polygamous
male bowerbirds: sexually dimorphic behaviours
males compete against one another to win over female mates
male bowerbirds have lots of different mating partners, and females raise offspring alone
so females must choose their mate wisely
males impress them by building colourful, elaborate bowers
sexual selection favours sexual ___________ and ____________ it over time
dimorphism
amplifies
sexually dimorphic behaviours are products of…
both NATURE and NURTURE
reflect role of biology and environment (socialization)
ie. boys are more likely to play in large groups, rough and tumble activities
ie. girls are more likely to play in twos and threes, more verbal communication
4 recaps from beginning of sexual differences lecture
- sex determination occurs in various steps
- sexual reproduction favours evolutionary flexibility by providing genetic variability
- possibly because of the mating system related to sexual reproduction, several behaviours are sexually dimorphic
- sexually dimorphic behaviours are a product of nature and nurture
5 levels of mammalian sexual differentiation
- chromosomal sex
- gonadal sex
- hormonal sex
- morphological sex
- behavioural sex
each level affects the next one
step 1 in process of mammalian sexual differentiation
chromosomal sex
chromosomal sex
defined during fertilization
chromosomal sex of the child = determined by whether the sperm contributes with an X or a Y chromosome (female gametes always contributes an X chromosome)
XX: female
XY: male
step 2 in process of mammalian sexual differentiation
gonadal sex
gonadal sex
testes or ovaries
each embryonic individual (regardless of chromosomal sex) develops a thickening called the GERMINAL RIDGE
this is a bipotential primordial gonad
expression of SRY gene (found on Y chromosome) produces testis determination factor (TDF)
location of germinal ridge
on the ventromedial surface of each protokidney
bipotential primordial gonad
this is what the thickening of the germinal ridge gives way to
bipotential: can either turn into ovaries or testes
depends on whether or not there is SRY gene
where is the SRY gene found? what does it produce?
found on the Y chromosome
produces TDF (testis determination factor)
SRY presence versus absence
presence: will produce TESTIS DETERMINATION FACTOR (TDF)
absence: no testis determination factor
testis determination factor (TDF)
produced by the SRY gene
SF-1
steroidogenic factor 1 protein
in combination with TDF, produces a transcription factor
this transcription factor regulates expression of SOX9 gene
SF1 + TDF =
transcription factor
this transcription factor regulates expression of SOX9 gene
protein products of SRY and SOX9 lead to…
development of the middle of the germinal ridge
this forms the testis
so development of the testis requires…
SRY gene
TDF
SF-1
transcription factor
SOX9
if SRY or SOX9 aren’t produced…
the outer part of the germinal ridge develops
and ovary forms
what part of germinal ridge develops if SRY and SOX9 are produced? what about if they’re absent?
if present: middle of the germinal ridge develops (into testis)
if absent: outer part of germinal ridge develops (into ovaries)
recent evidence suggests that _______ gene is required for normal ________ _____________
Wnt4 (wingless-related MMTV integration site 4) gene
ovarian development
discovery of Wnt4 gene is important because…
used to be thought that mere absence of SRY and SOX9 would cause female development (ovaries)
but turns out there is another gene that probably must be present (Wnt4 gene)
step 3 of mammalian sexual differentiation
hormonal secretions
hormonal sex
hormonal secretions from the developing gonads determine whether the individual develops in a male or female manner
mammalian embryonic testes produce ANDROGENS
embryonic ovaries of mammals don’t secrete high concentrations of hormones
in presence of ovaries or in complete absence of any gonads, the development follows female pathway
androgens =
no gonads/hormones =
male development
female development
mammalian embryonic testes produce…
androgens
embryonic ovaries don’t secrete…
high concentrations of hormones
interesting finding: sexually dimorphic transcription of over 50 genes in brains of mice at 10.5 days post-conception
50 chromosomal genes were different between males and females
even at 20.5 days post-conception
wayyyy before gonads were developed
suggests that sex genes = mediated by chromosomes, not gonads
interesting finding: cell culture from XY mice contain more cells expressing tyrosine hydroxylase than XX cultures, irrespective of the gonadal sex of the embryos from which the cells were taken
again, suggests that chromosomes are mediating sex to certain degree
independently from gonads
step 4 of mammalian sexual differentiation
morphological sex
morphological sex
Mullerian (female) and Wolffian (male) duct systems are normally BOTH PRESENT early in embryonic development
dual anlagen
dual anlagen
rudimentary basis of accessory sex organs
apparatus for both male and female accessory organs (“dual”)
both Wolffian and Mullerian
Mullerian duct system develops into…
fallopian tubes
uterus
upper vagina
and the Wolffian ducts regress
Wolffian ducts develop into…
seminal vesicles
vas deferens
Mullerian system regresses
what do male accessory sex organs require?
two products from the embryonic testes
- testosterone
- Mullerian inhibitory hormone (MIH)
what do testosterone and MIH do, respectively?
testosterone: stimulates Wolffian duct development (masculinization)
MIH: causes regression of the Mullerian duct system (defeminization)
what is responsible for the differentiation of the external genitalia?
androgens
what happens in the presence of androgens?
- urethral groove fuses
- genital tubercle develops into penis
- genital folds fuse into scrotum
what happens in absence of androgens?
- clitoris develops from genital tubercle
- vaginal labia develops from genital folds
are accessory sex organs differentiated at 6 weeks?
no, they’re undifferentiated
- genital tubercle
- urogenital sinus
- anal fold
male versus female external genitalia
male: penis, scrotum
female: clitoris, labia
what controls mating behaviour in both sexes?
gonadal steroid hormones
castration of male mice - effect on mating behaviour
castrated males stop mounting behaviour
but testosterone replacement therapy restores mounting behaviour to original levels
typical female versus male mating behaviour
female: lordosis
male: mounting
does injection of adult females with testosterone increase their mounting behaviour?
no, it does not
suggests that at some point in development, female rats lose potential to exhibit male-typical behaviour
do males injected with estrogen display female-typical behaviour?
no
first study that led to organizational/activational hypothesis of hormonal differentiation
Charles Phoenix
wanted to know at what point differentiation occurs
studied effects of PRENATAL and EARLY POSTNATAL androgen treatment on guinea pigs
on female reproductive behaviour (mounting/lordosis)
did this by observing and manipulating mating behaviour
Charles Phoenix study: Phase 1 setup
PHASE 1:
- pregnant guinea pig was injected with testosterone
- some received larger doses than others
female offspring from mother with larger dose…
possessed external genitalia indistinguishable from those of brothers/typical males
female offspring from mother with smaller dose…
no visible changes to external genitalia
referred to as “unmodified females”
Charles Phoenix study: Phase 2 three groups
looked at the adult offspring
- smaller dose prenatal testosterone exposed females and males
- bigger dose prenatal testosterone exposed females and males
- control females and males
Charles Phoenix study: Phase 2
all 3 groups were:
- gonadectomized
- injected with estrogen and progesterone
(to stimulate female sexual behaviour) - paired with male guinea pig
- some time later, were all injected with androgens (to stimulate male sexual behaviour)
- paired with female guinea pig
Charles Phoenix study: conclusion
androgens given to guinea pigs prenatally
- decreased tendency of both experimental groups of females to display lordosis in adulthood
- increased tendency of both experimental groups of females to display mounting behaviour in response to testosterone therapy
- caused no deleterious effects on mounting behaviour or other masculine behavioural patterns in males treated
Charles Phoenix study: important distinction that emerged
clear distinction can be made between PRENATAL ACTION of HORMONES in causing differentiation/ORGANIZATION of neural substrates for behaviour
and the actions of HORMONES in ADULTHOOD in causing ACTIVATION of these hormones
organization - activation hypothesis
Charles Phoenix study led to…
basis for the organizational/activational hypothesis of sexually dimorphic behaviours
organizational/activational hypothesis of sexually dimorphic behaviour
- sex hormones act during prenatal stage to permanently (irreversibly) organize the nervous system in a sex-specific manner
- during adult life, the same hormones have activation effects
cyclic versus tonic gonadal function
cyclic: present in females
- females display cycles of mating behaviour
tonic: present in males
- males display continuous willingness to mate
luteinizing hormone (LH) profile in females and males
females:
- pulsatile release
- then negative feedback is broken
- big increase of LH and FSH secretion
- after ovulation, neg feedback returns
males:
- steady pulsatile release
gonadal function (LH levels) is driven by…
gonadotropins secreted from the anterior pituitary
GnRH –> LH –> gonadal function
luteinizing hormone affects…
differences in males versus females…
testis and ovaries
testis: testosterone
ovaries: estrogen and progesterone
in females, the negative feedback control of GnRH secretion is altered on a…
cyclical basis
females escape the negative feedback loop on a cyclical basis
process of breaking the negative feedback loop
- females escape negative feedback loop on cyclical basis
- estrogen levels increase
- surge of GnRH is released in response to rising estrogen levels
- GnRH stimulates the anterior pituitary to release surges of LH and FSH
- after ovulation, negative feedback mechanisms are engaged
how does the negative feedback system work to regulate steroid secretion?
both males and females have this
increasing gonadal steroid concentrations feed back to the gonads, anterior pituitary and hypothalamus
this slows secretion of GnRH, gonadotropins and gonadal steroids
atypical sexual development
a lot happens in the process of sexual differentiation
because it’s a complicated process
high potential for atypical development
chromosomal to gonadal sex
SRY gene is located on the short arm of the Y chromosome
this gene causes male gonadal development
partial expression of SRY gene
leads to incomplete gonadal differentiation
chromosomal XY but no SRY
male mice develop ovaries
chromosomal XX but inserted SRY gene
female mice develop testes
Swyer syndrome
rare disorder
failure of sex glands (testis or ovaries) to develop
in XY individuals that lack SRY gene
without intervention, won’t experience puberty
external female genitalia, but no menstruation
gonads = functionless
what is Swyer syndrome classified as?
a disorder of sex development (DSD)
DSDs encompass any disorder in which chromosomal, gonadal or anatomic sex development is atypical
how is Swyer syndrome treated?
hormone replacement therapy
hormonal to morphological sex
even if individual is XY, testosterone and MIH must be secreted at the correct time
if MIH isn’t secreted at right time, the Mullerian syndrome will develop
depending on hormonal secretion, possible for both systems or for neither to develop
intersex
general term used for variety of conditions in which a person is born with reproductive/sexual anatomy that doesn’t fit the typical definitions of male or female
ie. discrepancies between external genitalia and internal sexual organs
ie. when both systems develop in a single individual (can be separate or combined)
is intersex considered a medical problem?
no, although it may signal underlying metabolic concern
intersex individuals aren’t in need of medical treatment
although it used to be considered one - “normalization” srugery
spectrum of hormonal to morphological sex
two continuum which intersect
- masculinization to de-masculinization
- feminization to de-feminization
potential for multiple different outcomes
Prader scale
scoring system for grading degrees of genital masculinization
starts at a 0: unvirilized female
ends at 5: completely virilized female
completely virilized female
5 on the Prader scale
female who appears externally male at birth with the labial/scrotal sac empty since there are no testicals
what is responsible for differentiation of external genitalia?
androgens
and androgenic metabolites
what androgenic metabolite of testosterone is critical for genital fusing process?
5 alpha-dihydrotestosterone (DHT)
testosterone is converted to DHT by an enzyme
in females, unusually high levels of DHT leads to…
development of male external genitalia
5alpha-reductase deficiency
genetic males (XY) with this deficiency are born with:
- ambiguous genitalia
- small, undescended testes
- usually considered females at birth, reared as females
- at puberty, testosterone masculinizes the body
what happens at puberty for XY individuals with 5alpha-reductase deficiency?
at puberty, testosterone masculinizes the body
- male-typical musculature
- axillary hair growth
- genitalia develop to resemble male-typical penis and scrotum
Turner syndrome
- congenital condition
- individuals LACK an X chromosome (XO) or DAMAGE to second X (or Y) chromosome
- have female external appearance
- but ovarian development = usually limited
- don’t attain puberty without medical attention
congenital adrenal hyperplasia
caused by lack of 21-HYDROXYLASE enzyme
leads to overproduction of ADRENAL ANDROGENS
- progesterone also needs 21-hydroxylase in order to create other important hormones
does congenital adrenal hyperplasia cause problems in congenital males?
no
what does congenital adrenal hyperplasia do to female genitalia?
causes moderate/sever masculinization
androgen insensitivity syndrome
functional androgen receptors are absent
XY individuals born with androgen insensitivity syndrome have normal-appearing female external genitalia
but vagina is oftenshort and they’re sterile
are sexed and reared as girls
people with androgen insensitivity syndrome are sexed and reared as…
girls
but vagina is short and no menstruation occurs (they’re sterile)
when do people discover that they have androgen insensitivity syndrome?
at adolescence
when menstruation fails to occur
3 possible trisomic anomalies
- Klinefelter syndrome (XXY)
- XYY
- XXX
Klinefelter syndrome
XXY
extra X chromosome
presence of Y chromosome = sufficient for SRY gene to be activated and for masculinization to occur
usually sterile because of reduced sperm production
often severe learning disabilities
people with Klinefelter syndrome are sexed as…
males at birth
Klinefelter syndrome seems to mainly reflect…
variation in the androgen receptor
MODERN organizational/activation hypothesis of sexual differentiation
expands the variables that influence sex differences:
1. genes
2. hormones
3. ENVIRONMENT
expands the amount of time in which organization effects take place
1. extend to pre-pubertal period
essentially, the modern theory sees things as much less fixed (more variables are at work and time period in which they have effects are longer)
average sex differences in behaviour often reflect significant overlap between the sexes…
are often greater differences in behaviour BETWEEN INDIVIDUALS OF THE SAME SEX
than between individuals of the opposite sex
considerable overlap between the sexes
gender role
what roles society expects genders to perform
gender identity
internal and personal process by which individuals come to perceive themselves
what they understand their own gender to be
binary, non-binary and plural
sexual orientation
enduring pattern of:
- emotional
- romantic
- and/or sexual
attractions that individuals feel towards people of the same and/or opposite sex
