Slide Set 3 Flashcards
2 basic types of physiological signals
Electrical : involve changes in membrane potential
Chemical : molecules secreted by cells into extracellular fluid
4 methods of cell-cell communication
Gap Junctions
Contact-dependent signals
Chemicals that diffuse
Long-Distance communication
Gap junctions
- simplest form of cell-to-cell communication
- direct transfer of E and C signals
- creates cytoplasmic bridges between adjacent cells
Which molecules can pass or can’t go through a gap junction
can : ions, amino acids, ATP, cAMP
can’t : large molecules
Connexins
= proteins on the membrane that connects the cell in a gap junction
What is the only means by which electrical signals can pass directly form cell to cell
gap junctions
Contact-dependent signals
- interaction between membrane surface molecules on 2 cells
- immune system, growth, development
- Cell-adhesion molecules (CAMs)
What are CAMs
= Cell-adhesion Molecules
Are present in contact-dependent signals
They transfer signals, like integrins
Chemical signalling
- paracrine : signals secreted by ONE cell and diffuse to the NEXT
- autocrate : signals act on the SAME cell that secreted them
Long-distance communication
- HORMONES
- NEUROTRANSMITTERS
- Cytokines
(also local signalling)
HORMONES
Long-distance
- secreted by endocrine glands/cells into the blood
- cells with RECEPTORS for the hormone (“lock & key”) will respond to the signal
NEUROTRANSMITTERS
Long-distance
= chemicals secreted by neutrons that diffuse across a small gap to the target cell
- use chemical and electrical signals
- have a rapid effect
Neurohormones
examples :
chemicals released by neutrons into the blood for action at a distant target
examples : norepinephrine and epinephrine
CYTOKINES
Local and long-distance signals
- all nucleated cells synthesise and secrete them
- control cell development, differentiation, immune responses
- have a broader action than hormones
- made on demand, not stored
Difference between cytokines & hormones
Cytokines act on a broader spectrum of target cells than hormones. Are like hormone but not produced by a gland, they are made on demand.
Signal pathways
- Ligand/first molecules brings info/signal to target cell
- Ligand-receptor binding activates the receptor
- receptor activates one or more intracellular signal molecules
- Last signal molecule initiates synthesis of target proteins or modifies existing target proteins to create a response
Signal molecule -> binds to __ -> activates intracellular signal molecule -> alters __ -> response
receptor protein
target proteins
Where are receptor proteins located
Inside cell or on the cell membrane
Location of ligand/receptor binding is dependant on whether a signal molecule is __ or __
hydrophobic or hydrophilic
__ signal molecules can diffuse through the phospholipid bilayer binding to __ or __ receptors
Hydrophobic
Cytoplasmic
Nuclear
Receptor activation often turns on or off a _
This is a relatively __ process
gene
slow
Lipophobic signal molecules __ diffuse through the plasma membrane
CAN’T
- they bind to extracellular receptors (on plasma membrane)
- causes a cascade of events
Lipophobic molecules
hydrophilic
- bind to extracellular receptors on plasma membrane
- very rapid response
Lipophilic molecules
hydrophobic
- diffuse through phospholipid bilayer
- bind to cytoplasmic or nuclear receptors
- slow process
(some can bind to membrane receptors in addition to intracellular receptors)
Why is the response slower for lipophilic signal molecules?
Because this is related to changes in genes activity,
the receptors bind in the nucleus
Where are receptors for lipophilic signal molecules?
- in cytosol
- in nucleus
Signal pathway of lipophobic signal molecules
- bind to cell membrane receptor
- forms ligand-receptor complex
- rapid cellular response :
- Initiates transduction by proteins
- second messenger
What is the role of the second messenger
- alters gating of ion channels
- increases intracellular calcium
- changes enzyme activity (protein kinases, protein phosphatases)
Steps of signal transduction pathway form a __
CASCADE:
inactive A becomes active A thanks to a stimulus, leased to inactive B becoming active B etc until product
Example of receptor-enzyme
tyrosine kinase
- is on the cytoplasmic side
- it transfers a phosphate group from ATP to a tyrosine of a protein
Peptide hormones are lipophilic or lipophobic?
ex: insulin, glucagon, leptin, ADH, oxytocin
Lipophobic : they can’t cross freely the plasma membrane
What do most signal transduction use?
G proteins
They bind nucleotide guanosine
G protein coupled receptors
Membrane spanning proteins that cross phospholipid bilayer 7 times
When activated, they open ion channels in the membrane and alter enzyme activity on the cytoplasmic side of the membrane
GPCR : Adenyl Cyclase - cAMP
- signal molecule binds to G protein-linked receptor, activates G protein
- G protein turns on adenylyl cyclase, an amplifier enzyme
- Adenylyl cyclase converts ATP to cyclic AMP
- cAMP activate protein kinase A
- PKA phosphorylates other proteins, leading to a cellular response
GPCR : Phospholipase C system
- signal molecule activates receptor and associated G protein
- G protein activates phospholipase C an amplifier enzyme
- PLC converts membrane phospholipids into diacyglcyerol which remains in the membrane, and IP3, which diffuses into the cytoplasm
- DAG activates protein kinase C which phosphorylates proteins
- IP3 causes release of calcium from organelles, creating a calcium signal
Which enzymes is responsible for phosphorylation go other proteins?
Protein kinase A, C
Signal pathway : receptor channel
- ion channels also serve for signal transduction
- extracellular ligand binds to the receptor - channel protein, a channel gate opens or closes
- initiates most rapid response
Between receptor-channel, PLC, AC-cAMP transduction, which initiates the fastest response?
receptor-channel
Calcium ions
- versatile intracellular messenger
- second messenger
- enter through voltage-gates calcium channels or ligand/mechanically gated channels
- inside, calcium can bind to calmodulin which alters protein activity
- inside, calcium can also bind other proteins
A change in ion concentration inside the cell creates
electrical signal
this triggers release of calcium from organelles
An agonist and primary ligand ->
activates a receptor -> response
An antagonist ->
blocks the receptor activity -> no response
Endocrine and nervous system
- function to achieve and maintain homeostasis
- are connected
- communication, integration, control
- when work as one system = neuroendocrine system
Endocrine system
- wireless
- glands aren’t linked with their target cells
- chemical messengers are secreted into blood and delivered to DISTANT target sites
Nervous system
- each nerve cell terminates on a specific target cell
- wired for specific transmission to a target
- neutrons can release neurohormones into the blood instead of neurotransmitters
Differences btwn endocrine and nervous system
- neurotransmitters : rapid effects, are short lived
neurons can stimulate only muscles and glands across a synapse - hormones : slow, longer lasting, diffuse in blood and can access most tissues and cells
Important feature of nervous system
NEURAL SPECIFICITY
- muscle movement depends on which neuron releases Ach
Endocrine glands
- endocrine glands : synthesise and secrete hormones
= “ductless glands” widely scattered in body - a few are made of neurosecretory tissue => neurons don’t always secreted chemical messengers across a synapse
Exocrine glands
= secrete product
Endocrine glands examples:
- hypothalamus
- anterior pituitary
- posterior pituitary
- pineal glad
- thyroid gland
- adrenal cortex
- pancreas
- gonads
Function of :
- hypothalamus
= MASTER gland
- receives input
- controls release of pituitary hormones through realising/inhibiting factors
Function of :
- anterior pituitary
- TSH (thyroid stimulating hormone)
- ACTH (adrenocorticotropic hormone)
- GH (growth hormone)
- FSH (follicle-stimulating hormone) & LH (luteinizing hormone)
- PRL (prolactin)
- MSH (melanocyte stimulating hormone)
Function of :
- posterior pituitary
- vasopressin : antidiuretic hormone acts on kidneys
- oxytocin : milk let down and uterine contractions
ACTH
= adrenocorticotropic hormone
stimulates cortisol secretion from adrenal cortex
GH
= growth hormone
growth and metabolic effects
FSH & LH
= follicle-stimulating hormone & luteinizing hormone
FSH & LH
= follicle-stimulating hormone & luteinizing hormone
act on gonads, growth of follicles, ovulation
PRL
= prolactin
milk synthesis from mammary glands
Function of :
- pineal glands
produce melatonin
> controls biological (circadian rhythm)
Function of :
- thyroid glands
produce T3, T4 & calcitonin to decrease plasma.
controls how quickly body burns energy, makes proteins
=> metabolism regulator
Function of :
- adrenal cortex
produces :
- mineralocorticoids
> aldosterone -acts on kidney conserve sodium, retain water
- corticosteroids
> cortisol - increase BP and blood sugar, reduces immune response, anti-inflammatory
> androgens - DHEA (sex steroids)
Function of :
- adrenal medulla
produces : epinephrine and norepinephrine
=> stress adaptation
Function of :
- pancreas
produces : - insulin - glucagon - somatostatin => nutrient levels and utilisation
Function of :
- gonads
testies: produce testosterone
ovaries : produce estrogen & progesterone
Iodine deficiency
-> swollen neck because iodine is not present
iodine is essential for production of T3
coq: physical growth and development problem, mental impairment
T3 and T4 are primarily composed of
iodine
Calcitonin
helps reduce calcium concentration in blood
Grave’s disease
- hyperthyroidism
- immune system makes an antibody (TSI - thyroid stimulatory immunoglobulin) that attaches to thyroid cells. It acts like TSH and stimulates thyroid gland to produce T3 and T4.
Classification of hormones
- structure
- function
Structural classification of hormones
- HYDROPHILIC
> peptide or protein hormones (insulin, catecholamines : epinephrine) - LIPOPHILIC
> thyroid hormones and steroids (steroids are derived from cholesterol)
Functional classification of hormones
- TROPIC hormones > target other endocrine glands and stimulate their growth and secretion of other hormones > ACTH targets the adrenal cortex - SEX hormones > target reproductive tissues - ANABOLIC hormones > stimulate anabolism (build up) in target cells > testosterone
Hormone __ determines the way it is transported in the blood, the means by which the endocrine cell processed it, the mechanism by which it effects signalling
solubility
Are all hormones transported in the blood? The same way?
Yes in the blood
Not the same way
Hydrophilic hormones
In plasma: are dissolved
Bind : to receptors on the surface of target cells
Lipophilic hormones
In plasma : are bound to plasma proteins
Bind : pass through target cell membranes and bind to receptors inside the target cell
Preprohormones
= hydrophilic peptide hormones precursors
- made on ribosomes of ER
- converted to prohoromones in Golgi -> active hormones
- released by exocytosis
Precursor for all steroid hormone -lipophilic (except thyroid hormones)
Cholesterol !
- the precursor is stored
- the lipid soluble hormone is not stored or excreted in urine
From preprohormone to secreted hormone
Preprohormone (ribosome) -> prohormone (ER) -> Golgi -> release
Precursor for thyroid amine hormones
Tyrosine
These hormones are stored until they are secreted
Steroid hormone synthesis
- synthesised from cholesterol
- have a 4 ring steroid nucleus
- Lipid soluble
- pass through plasma membrane of target cells bind to nuclear receptors (at HRE - hormone response element) to initiate gene transcription
Steroid hormones examples
- cortisol, aldosterone (= adrenals)
- estrogen (ovary & testis)
- progesterone (ovary-CL)
- testosterone (testis - Leydic cells)
Non-steroid hormone synthesis
- synthesised form amino acids
- some are :
> protein hormones
> glycoprotein hormones
> peptide hormones
> amino acid derivative hormones
Protein hormones
= long, folded chains of aa
ex: insulin
Glycoprotein hormones
= protein hormones with CARBOHYDRATE groups attached to the aa chain
ex: hCG (human chorionic hormone-pregnancy recognition)
Peptide hormones
= smaller than protein hormones, short chain of aa
ex: oxytocin, antidiuretic hormone (ADH)
Amino acid derivative hormones
= derived from a single amino acid molecule
> amine hormones - modifying tyrosine, produced by neurosecretory cells and neurones
ex: epinephrine, norepinephrine (adrenal medulla)
> adding iodine to tyrosine
ex: thyroxine (T4)
General principles of hormone action
- bind to target cell’s specific receptor in a “lock & key” mechanism
- hormone-receptor interaction produce different regulatory changes (inactivation of an enzyme, initiation of gene transcription)
Combined hormone actions
- synergism : combinations of hormones acting together to have a greater effect on a target cell than if acted alone
- permissiveness : when small amount of 1 hormone permits or enables a second one to have its FULL effects on a target cell
- antagonism : one hormone produces the opposite effects of another hormone
Which hormones demonstrate “permissiveness”
thyroid hormones are always present when development
Which hormones demonstrate “antagonism”
parathyroid hormone : increases blood calcium
calcitonin : thyroid decrease blood calcium
Most hormones have :
- primary effect ->
- secondary effects ->
-> directly regulate target cells
-> influence or modulate other regulatory mechanisms in target cells
ex: prolactin
1° effect - stimulates mammary gland cells to transcribe milk proteins
2° effect - on immune cells
Hormone actions must be __
terminated
- they have a half-life
- are degraded into inactive metabolites in the liver
Where are steroid hormones’ receptors? Responses to steroid hormones are often __
In nucleus or cell’s cytosol.
SLOW
What does sensitivity of target cells depend on
number of receptors
up-regulation
increased number of hormone receptors
increases sensitivity-hormones often regulate own receptor levels
down-regulation
decreased number of hormone receptors decreases sensitivity
Mechanisms of hydrophilic-protein and peptide hormones
- second messenger mechanism : produces target cell effects that differ from steroid hormone effects
> effects of hormone are amplified by cascade of reactions
> much faster than steroid mechanism
Non steroid hormones usually operate in __
second messenger mechanism
- hormone molecule = first messenger
- delivers chemical message to fixed receptors on plasma membrane
- message passed by G protein into cell, where second messenger triggers the appropriate cellular changes
Examples of second messengers
- cAMP :
adenylyl cyclase -> cAMP -> activates PKA -> induces protein to change shape
ex: FSH - calcium (still binding of G protein linked receptor)
phospholipase C -> IP3 -> calcium -> calmodulin -> induces protein to change shape
ex: oxytocin
Regulation of hormone secretion
= negative feedback loop (reverses deviations from set points)
endocrine gland : sensitive to physiological changes or regulated by a hormone produced by another gland
Humoral status can also regulate hormones
lactation > blood calcium concentration decreases > sensed by parathyroid > parathyroid increases secretion of parathyroid hormone (PTH) > PTH stimulates osteoclasts in bone to release more calcium from storage in bone tissue > increases maternal blood calcium concentration to the set point level
Pituitary Gland
- very small (1.2-1.5cm)
- well protected
- INFUNDIBULUM - connects pituitary to hypothalamus
- made of 2 glands : anterior & posterior
Anterior pituitary
- 2 parts : pars anterior and pars intermedia
- tissue composed of irregular clumps of secretory cells supported by fine connective tissue fibres and surrounded by a rich vascular network
- makes growth hormone, adrenocorticotropic hormone, thyroid stimulating hormone, gonadotropic hormones, prolactin
5 functional types of secretory cells in adenohypophysis
1- somatotrophs : secrete GH 2- corticotrophs : secrete ACTH and MSH 3- thyrotrophs : secrete TSH 4- lactotrophs : secrete prolactin 5- gonadotrophs : secrete LH and FSH
GH - Growth hormone
- promotes growth of bone, muscle, other tissues
> by stimulating liver to produce growth factors that accelerates amino acids transport into cells - stimulates lipid metabolism
> accelerates mobilisation of lipids from cells and speeds up lipid catabolism
> hyperglycemic effect
Hyperglycemic effect of GH
Insulin-growth factor (IGF) released from the liver in response to GH
- increases BG
- enhances lipid catabolism
- promotes protein anabolism
When does prolactin come?
- during pregnancy : promotes development of breasts, anticipating milk secretion
- after baby is born : stimulates mammary glands to produce milk
Tropic hormones
= hormones that have a stimulating effect on other endocrine glands
What are the 4 principal tropic hormones produced and secreted by basophils of the pars anterior ?
- thyroid stimulating hormone
- adrenocorticotropic hormone
- Follicle stimulating hormone
- Luteinizing hormone
What happens to FSH levels at menopause?
- rise of FSH, it stays high for the rest of life
it tries to grow a follicle but it can’t
Hypothalamic regulatory hormones reach ant pituitary by a __
capillary-capillary connection = hypothalamic hypophyseal portal system
From hypothalamus to anterior pituitary gland
Hypothalamus > secretes releasing hormones into blood > carried to hypophyseal portal system > anterior pituitary gland
Hormones released by hypothalamus
(RH: releasing hormone - IH : inhibiting hormone)
- GHRH - growth hormone RH
- GnRH - Gonadotropin RH
- CRH - Corticotropin RH
- TRH - Thyrotropin RH
- PRH - Prolactin RH
- PIH - Prolactin IH
- GHIH - Growth hormone IH
__ carries blood from hypothalamus directly to adenohypophysis where target cells of releasing hormones are located
hypophyseal portal system
Anterior pituitary =
Posterior pituitary =
= adenohypophysis
= neurohypophysis
What is the relationship between hypothalamus and posterior pituitary ?
hypothalamus : has neurosecretory cells’ body
posterior pituitary : has neurosecretory cells’ axon terminals
What does the posterior pituitary release? (2)
- OXYTOCIN
- VASOPRESSIN (ADH - antidiuretic hormone)
Hormone pathologies occur when
- hormone excess
- hormone deficiency
- abnormal responsiveness of target tissues
Hormone excess
ex: hypercortisol secretion = Cushing’s disease
cause = tumour of adrenal gland secreting cortisol or tumour secreting acth -> stimulates excessive secretion of cortisol
symptoms = breakdown of muscle proteins, redistribution of body fat, red and round face
Hormone deficiency
ex: hypothyroid secretion
causes = iodine deficiency, stress
symptoms = swelling of facial tissues, low body temp, sensitivity to cold, dry skin and hair, slow heart rate
Abnormal responsiveness of target tissues
ex: type 2 diabetes mellitus (loss of tissue sensitivity to insulin)
causes = obesity
symptoms = high blood glucose, weight loss, excessive thirst, frequent urination
Type 1 diabetes mellitus :
Type 2 diabetes mellitus :
1: loss of insulin production
2: loss of tissue sensitivity to insulin
Neuroendocrine system adjusts
nutrient supply
Calcitonin , parathyroid hormone, vitamin D balance __
calcium ion use
Nervous system and hormones regulate _
Reproduction
