Endocrinology Flashcards
How do positive feedback loops influence the parameter?
pushes the parameter further from the set point
how do negative feedback loops influence the parameter?
bring the parameter closer to the set point
What are the 4 types of feedback regulation?
direct feedback loop
first-order
second order
third order
Describe direct feedback loops
the tissue/organ that senses the parameter change is the same one that releases the hormone that will cause a response from the target organ to bring the parameter closer to the set point
describe first order feedback loops
sensor sends a signal messenger (neurotransmitter) to the integration centre which sends a messenger (neurotransmitter) to the target organ which produces a response to bring the parameter closer to the set point
describe second order feedback loop
the sensor sends a messenger (neurotransmitter) to the integration centre which sends a message (neurotransmitter) to the endocrine gland which releases a hormone into the circulatory system to the target organ to elicit a response to bring the parameter closer to the set point
Explain how there’s 2 negative feedback loops in second order feedback loops
there’s one that includes the entire system from the response to the stimulus
the endocrine gland has it’s own negative feedback loop: the response from the target organ can negatively regulate the endocrine gland and the hormones it releases
describe third order feedback loops
the sensor organ sends a neurotransmitter to the integrating centre which sends a neurotransmitter to an endocrine gland which releases a hormone into the circulatory system
this causes a second endocrine gland to release a second hormone into the circulatory system to find the target organ
target organ responds to bring the parameter closer to the set point
How does a third order feedback loop have 3 points of regulation?
there’s 3 negative feedback loops
1 for the entire system
1 from the response to the first endocrine gland
1 from the response to the 2nd endocrine gland
What’s a major difference between direct feedback regulation and different ordered loops?
direct feedback loops only involve endocrine glands, whereas the ordered loops involve the nervous system (neurons and neurotransmitters)
In direct regulation, what could be the sensor organ?
an endocrine gland could sense the stimulus and also release the hormone directly into the circulatory system to reach the target organ
Explain how the atrial natriuretic peptide is an example of direct feedback regulation
the atrium is the sensor that senses the high blood pressure and releases the atrial natriuretic peptide hormone to stretch the cells of the atrium and lower blood pressure
organ is both sensor and releaser of hormone
What are the 2 anatomic sections of the pituitary gland?
anterior pituitary (adenohypophysis)
posterior pituitary (neurohypophysis)
What part of the brain is the pituitary gland connected to? explain how
hypothalamus
the neurons that grow into the posterior pituitary gland originate in the hypothalamus
the cell bodies are in the hypothalamus and the axons extend into the posterior pituitary
What type of feedback regulation occurs in the pituitary gland? explain
first order endocrine pathway
hypothalamus senses a stimulus and acts as the integrating centre to send information to the posterior pituitary gland (target organ) via a neuron causing the pituitary gland to release a hormone into the blood causing a response
Explain how oxytocin is released and regulated by the endocrine system
first order positive feedback loop
oxytocin stimulates uterine contraction during child birth
fetus presses against uterus = stimulus
cervix stretch cells (sensor) receive signal and send neurotransmitter to hypothalamus (integrating)
hypothalamus sends a neurotransmitter via a neuron to the posterior pituitary gland (target organ)
posterior pituitary gland releases oxytocin into the blood stream to increase uterine contractions
this response causes a stronger signal to be sent to the stretch cells of the cervix to increase the release of oxytocin and cause more contractions = pushes the parameter further from the set point (positive feedback)
What order of endocrine pathways (feedback regulation) is the anterior pituitary gland involved in?
second and third order
Explain the endocrine pathway the anterior pituitary gland is involved in
second and third order
sensor: hypothalamus senses stimuli and releases neurohormones to the
integration center: hypothalamus-pituitary portal system which releases another hormone to
endocrine gland/target organ: anterior pituitary releases a hormone into the circulatory system to cause a response
What’s a tropic hormone?
a hormone that causes the release of another hormone
What are the 3 neurohormones (tropic hormones) that the hypothalamus will release to reach the anterior pituitary?
prolactin-releasing hormone (PRH)
prolactin-inhibiting hormone (PIH/dopamine)
corticotropin-releasing hormone (CRH)
describe the endocrine pathway related to the prolactin-releasing hormone (PRH)
sensor: hypothalamus senses stimulus and releases PRH
integration centre: hypothalamus-pituitary portal system
endocrine gland: PRH stimulates the anterior pituitary to release prolactin (PRL)
target organ: prolactin stimulates breast tissue to produce breast milk
this is second order positive feedback (prolactin production causes breast milk production which increases the signal and causes the parameter to move further from the set point)
describe the endocrine pathway related to the prolactin-inhibiting hormone (PIH/dopamine)
sensor: hypothalamus senses stimulus and releases PIH
integration centre: hypothalamus-pituitary portal system
endocrine gland: PIH inhibits the anterior pituitary to stop the release of prolactin into the blood stream
target organ: prolactin does not reach the breast tissue and the lack of response causes the parameter to come back to the set point
negative feedback second order
describe the endocrine pathway for the corticotropin-releasing hormone (CRH)
sensor: hypothalamus senses stimuli and releases CRH
integrating: hypothalamic-pituitary portal
endocrine gland: CRH stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH) into the circulatory system
2nd endocrine gland: ACTH stimulates the adrenal cortex to release cortisol (hormone steroid) into the circulatory system
target organ: multiple
positive third order regulation
related to stress response
What endocrine function does the pancreas have?
blood-glucose regulation
Describe the cellular structure of the pancreas and its relation to glucose and blood-glucose levels
alpha cells produce glucagon
beta cells produce insulin
Why is the regulation of blood glucose levels essential?
glucose provides energy for brain cells so having a balanced level of blood-glucose is essential for brain function
What are the consequences of low blood glucose levels?
brain cannot function
What are the consequences of high blood glucose levels?
the osmotic balance of blood is disturbed
Which 2 hormones are involved in controlling blood-glucose levels?
insulin to lower blood glucose levels
glucagon to raise blood glucose levels
What does insulin do?
lower blood-glucose levels
What does glucagon do?
raise blood glucose levels
Who won the Nobel prize for discovering insulin?
Frederick Banting and John Macleod of University of Toronto in 1923
What endocrine organ secretes the hormones insulin and glucagon?
pancreas
What type of feedback loop/regulation is involved in the pancreas’s regulation of blood-glucose levels?
direct feedback loops
the pancreas receives neural and hormonal signals and releases hormones to trigger a response
What is antagonistic pairing?
when hormones have opposing effects
ex. insulin and glucagon
How does the pancreas reduce elevated blood glucose levels?
by secreting insulin
How does the pancreas increase lowered blood glucose levels?
by secreting glucagon
How many amino acids make up insulin?
51
How many amino acids make up glucagon?
29
What are the 2 major functions of the pancreas?
exocrine: secretes digestive enzymes
endocrine: secretes insulin and glucagon
What are the Islets of Langerhans?
clusters of cells in the pancreas with endocrine function (secrete insulin and glucagon)
What are the 2 types of cells found in Islets of Langerhams in the pancreas?
Beta cells: secrete insulin
alpha cells: secrete glucagon
Describe the endocrine pathway that follows elevated blood-glucose levels
direct feedback loop
sensor: pancreas receives signal that blood-glucose levels are high and releases insulin into the circulatory system
insulin causes:
glucose to be transported into beta cells via the glucose transporter GLUT2 = increases glucose in the cells and increases intracellular ATP
increased ATP closes ATP-dependent potassium channels
membrane potential is depolarized = activates voltage-gated Ca2+ channels
vesicles fuse and insulin is secreted into the blood
insulin binds to insulin receptors (RTKs)
the receptor tyrosine kinase signal transduction pathway causes phosphorylation of GLUT4 intracellular glucose transporters
GLUT4 translocates to the cell surface and glucose is transported out of the cell
What are the glucose transporters involved when insulin is released?
GLUT2 transporters bring glucose from the bloodstream into the beta cells of the pancreas
GLUT4 translocates to the cell surface to move glucose out of the cell and into muscle and fat tissue
Describe the endocrine pathway that follows lowered blood-glucose levels
direct feedback loop
sensor: pancreas receives signal that the blood-glucose levels are too low and releases glucagon into the circulatory system
glucagon is released by alpha cells in the pancreas and binds to G-protein coupled receptors in the liver (G alpha s)
activated Gas stimulates adenylate cyclase signal transduction
PKA activated
PKA phosphorylates glycogen phosphorylase kinase which breaks down glycogen (storage form of glucose) into glucose
GLUT2 carries glucose out of the cell and into the bloodstream
Which glucose transporters are involved in the release of glucagon?
GLUT2 carries glucose out of the cell into the blood stream
What is glycogenolysis?
the breakdown of glycogen into glucose
What is gluconeogenesis?
the formation of glucose
Why does glucose require transporters to bring it across cell membranes?
glucose is hydrophilic and cannot pass the hydrophobic membrane on its own
what’s the resting level of glucose?
4-6 mM
What’s the level of glucose after eating?
9-11 mM
What are the different isoforms of glucose transporters?
GLUT 1, 2, 3, 4
Where does GLUT1 function and how does it function?
in all tissues
constantly working on cell surfaces
Where does GLUT3 function and how does it function?
only in the brain
works constantly
Where does GLUT4 function and how does it function?
intracellular in muscle and fat tissue
involved in bringing glucose out of the beta cells and into fat and muscle tissues by translocating to the cell surface when insulin has been released to lower blood glucose levels
Where does GLUT2 function and how does it function?
in pancreatic beta cells and liver
brings glucose into and out of the beta cells
Which of the 2 hormones stimulates glycogenolysis and gluconeogenesis?
glucagon
Describe the insulin regulating pathways that occurs when you’ve eaten a meal
eat a meal
- increased blood glucose signals to the pancreas and the pancreas secretes insulin into the circulatory system to negatively regulate the blood glucose levels and lower them (direct)
- the glucose receptors in the digestive tract bind glucose and release CCK into the bloodstream > CCK stimulates secretion of insulin into the bloodstream by the pancreas > lowers blood glucose levels (2nd order)
- stretch receptors in the digestive tract sense increased glucose and send a signal to the integrating centre which sends a neuronal message to the pancreas > pancreas releases insulin into the blood stream and lowers blood glucose (2nd order)
Describe the antagonistic pairing in the regulation of blood-glucose that work to reduce glucose levels
when there’s an increase in blood glucose levels:
STIMULATING:
beta cells of pancreas are stimulated
increase of insulin secretion
target tissues increase uptake of glucose
blood glucose levels reduced
sends negative feedback to the sensor
INHIBITING:
alpha cells of pancreas stimulated
decreased glucagon secretion
target tissues reduce glucose release
blood glucose levels reduced
sends negative feedback to sensor
Describe Type 1 Diabetes Mellitus
occurs when blood-glucose levels are abnormally high due to lack of insulin production because the beta cells of the pancreas are attacked and destroyed (autoimmune)
10% of diabetics, usually diagnosed at young age
it’s insulin-dependent diabetes
alpha cells are spared
is type 1 diabetes the autoimmune disease? how is it treated?
yes, the beta cells of the pancreas are attacked and destroyed
treated with insulin injections
What mediates the destruction of the beta cells when someone has type 1 diabetes?
T cell lymphocytes
Describe Type 2 Diabetes Mellitus
non-insulin dependent diabetes
80-90% of diabetics, often diagnosed later in life
often related to other health factors such as obesity
blood-glucose levels are too high because cells become unresponsive to insulin (insulin resistance) as a result of impairment to the insulin receptor or the transduction mechanism causing beta cells to stop secreting insulin
What’s the major differences between type 1 and 2 diabetes?
Type 1 is insulin-dependent, type 2 is not
Type 1 is an autoimmune disease in which the beta cells are destroyed and cannot produce insulin to lower blood-glucose ; type 2 is not an autoimmune disease, likely due to an impairment in the signal transduction pathway of insulin secretion that prevents beta cells from secreting insulin
~10% of diabetics are insulin-dependent, type 1
~80-90% are NID, type 2
Describe how glucose levels are controlled in crustaceans
Low hemolymph-glucose causes:
Crustacean hyperglycemic hormone (CHH) to be released from the crab’s eyestalk (X-organ/sinus gland)
CHH binds to receptor guanylate cyclase
higher cGMP levels activate signaling pathway to release glucose and raise glucose levels (negative feedback)
under anaerobic conditions, glycolysis and lactate release cause the release of CHH
How does CHH regulate hemolymph glucose levels?
low glucose = increased CHH
high glucose = decreased CHH
low lactate = decreased CHH
high lactate = high CHH
How are lactate, glucose, and CHH related in crabs in a positive feedback loop?
low glucose levels cause build of lactate which increases CHH levels to release more glucose and increase glucose levels
How are glucose and CHH related in crabs in a negative feedback loop?
low glucose stimulates guanylate cyclase to stimulate glycogenolysis to breakdown glycogen and release glucose
high glucose levels inhibit guanylate cyclase and prevent glycogenolysis and the release of glucose
Which two physiological systems interact to stimulate the fight-flight response to stress in vertebrates?
the sympathetic nervous system and the hypothalamus-pituitary-adrenal cortex (HPA axis) of the endocrine system
Explain how the sympathetic nervous system is involved the vertebrate stress response
sense organ: brain receives stress signal and activates the sympathetic nervous system
a) sympathetic nerves increase heart rate, respiration, airway dilation
b)
What are the 4 major vertebrate stress responses onset by the sympathetic nervous system?
- SNS activates pancreas to decrease insulin secretion = increase blood-glucose
- SNS activates pancreas to increase glucagon secretion = increase blood-glucose
- SNS activates adrenal medulla to increase epinephrine in blood = increase heart rate, respiration, airway dilation, blood glucose levels, and to redistribute blood flow
- SNS directly targets other tissues to have the same physiological responses
these work together to increase delivery of nutrients, glucose and oxygen to fuel the body for survival
How does the endocrine system function in vertebrate stress response?
the brain senses the stressful stimulus
hypothalamus secretes corticotropin-releasing hormone (CRH)
CRH targets the anterior pituitary and causes the release of adrenocorticotropic hormone (ACTH)
ACTH activates the adrenal cortex to release cortisol
increased cortisol causes many cells in tissues to increase blood glucose levels
Describe additivity
a target cell’s response to combinations of hormones is the sum of the responses to the individual hormones
Ex. the glucose secretion caused by just glucagon + glucose secretion caused by just epinephrine = the glucose release when the two are combined
Describe synergism
When hormones increase the effect of other hormones and the response by the target cell to combinations is more than additive
ex. cortisol has a really small effect on glucose secretion, but when combined with glucagon + epinephrine, the result is significantly higher than if the individual responses were added up
What hormones does the adrenal cortex release?
cortisol, aldosterone
Where is the adrenal cortex? What type of cells exist there?
in the outer shell of the adrenal gland on the kidney
interrenal cells
Where is the adrenal medula? what type of cells exist there?
the inner layer of the adrenal gland on the kidney
chromaffin cells
What type of hormones does the adrenal medula secrete?
epinephrine (adrenaline)
What are circadian rhythms?
the mechanisms that control behaviour, activity, and physiology in response to light and dark periods (periodic activity)
What physiological parameters are controlled by circadian rhythms?
activity
body temperature
hormones
metabolism
sleeping/waking
feeding
What are circadian rhythms in sync with?
light and dark cycles, roughly over 24 hours
What part of the brain has been linked to circadian rhythms?
suprachiasmatic nucleus of the hypothalamus
How did researchers discover the connection between the suprachiasmatic nucleus and circadian rhythms?
used a control mouse with no surgery etc and found that activity was mostly during the dark periods of 12 hours and little during the light 12 hour periods
blind mouse, no surgery: activity still followed 12 hour cycles of activity and no activity though over time started to drift more into the light periods = still maintained circadian rhythm
mouse with SCN lesion: constant activity and no connection to 12 hour cycles or periods of light or dark = lose circadian rhythm
Explain the study on circadian rhythm in reindeer in the Arctic (both the 70 and 78 degrees north)
in the 70 degrees north population:
there were shorter periods of no light or all light
animals were still relatively rhythmic in their activity
in the 78 degree north:
in periods of 24 hours of darkness, the animals lost their circadian rhythms and were less active regardless of the time of day
in periods of 24 hours of light, the connection to their circadian rhythms were also disrupted as the animals were much more active regardless of time
How is the circadian clock in the SCN generated?
by a rhythmic cycle of changes to gene expression regulated by a negative feedback loop
What are the transcription factors involved in regulating the gene expression involved in circadian rhythms?
BMAL1 and CLOCK
Describe the steps involved in the negative feedback loop of gene expression involved in regulating circadian rhythms?
BMAL1 and CLOCK (transcription factors) heterodimerize
the heterodimer binds to E-box activator sequence located in the promoters of period (per) and cryptochrome (cry) genes
this produces proteins PERs and CRYs which heterodimerize in the cytoplasm
PER:CRY translocate into the nucleus to inhibit CLOCK:BMAL1 activity = inhibit PER:CRY transcription
because transcription is involved, there’s a time lag and PER and CRY increase or decrease cyclically
Describe what’s occurring in the SCN during the circadian day
BMAL1:CLOCK dimer actively binding to E-box and transcribing period and cryptochrome genes
this takes a long time to produce the protein products
Describe what’s occurring in the SCN during the circadian night
When transcription of period and cryptochrome genes is complete, the protein products CRY and PER heterodimerize in the cytoplasm and are translocated to the nucleus to inhibit the binding of BMAL1:CLOCK to the activator E-box sequence
prevents more transcription
Are circadian clock genes positively or negatively regulated?
negative feedback regulation on the transcription of circadian clock genes period and cryptochrome
