Lecture 4: Posterior Pituitary and HPL Axis Flashcards
What differentiates a preprohormone from a prohormone?
signal peptide
AVP associates with neurophysin ___
II (has 2 names - vasopressin, ADH, goes with NPII)
Oxytocin associates with neurophysin ___
I
Where are the cell bodies for AVP located?
In the PVN (paraventricular) and SON (supraoptic)
What are the 2 types of cells in the PVN?
1) magnocellular
2) parvocellular
Which type of neuron projects into the posterior pituitary?
magnocellular
Where do parvocellular PVN neurons project?
median eminence
regulate mood/anxiety/stress
When is neurophysin cleaved from AVP and oxytocin?
cleaved from prohormone in secretory granules during axonal transport
AVP release increase when plasma osmolarity __________
increases
which comes first, AVP release or thirst sensation?
AVP release
AVP release is tonically inhibited by what?
baroreceptor stretch and firing
decreased stretching during hypotension so you get DISINHIBITION
When plasma osmolarity increases, do osmoreceptors swell or shrink?
SHRINK (inducing AVP release)
GaqPCR stimulates ____
Ca++ (leads to vasoconstriction)
What receptors and where does AVP act?
V2 receptors on the kidney
What does AVP action do in the principal cells of the distal tubule?
phosphorylate aquaporin 2 to move these channels to the apical membrane
SHORT term: quick relocation, not synthesis
LONG term: makes more aquaporin
What are the 2 causes of diabetes insipidus?
1) decreased AVP release
2) decreased renal responsiveness to AVP
(AVP release defect is more common)
What causes diabetes insipidus?
AVP release problem: trauma, infectious disease
Renal responsiveness problem: genetic problem w/ receptor, lithium, hypokalemia
How do you tell the difference between the two causes of diabetes insipidu?
measure AVP levels (if normal, renal problem)
What does oxytocin do?
1) target smooth muscle in breast to stimulate milk ejection
2) stretch the cervix at the end of pregnancy
3) cuddling hormone
What stimulates the production of more oxytocin?
- more suckling
- more contractions
What synthetic hormone is used to stimulate labor?
Pitocin (oxy synthetic)
What is the oxytocin receptor?
GPCRaq
What effects does oxytocin have on the cell?
increase IP3 and increase calcium to increase MLC myosin ATPase activity
Which axis regulates growth?
HPL axis
H = arcuate nucleus GHRH
P = somatotrope GH
L = liver IGF-1
Where is GHRH produced in the hypothalamus?
arcuate nucleus
What inhibits GHRH at the level of the hypothalamus?
somatostatin
also inhibits GH and TSH in the pituitary
Where is somatostatin produced?
1) D cells in the stomach and duodenum (SS28)
2) PVN of the hypothalamus (SS14)
What effect does somatostatin have on GHRH in the hypothalamus? pituitary?
decreases frequency of pulses
pituitary: inhibits GH release when there is enough circulating
There is an _________ relationship between GHRH and somatostatin?
inverse
When during the day does GH peak?
at night during sleep
Many downstream target organ effects of GH are mediated through ________
IGF-1
production is stimulated by GH
Describe the negative feedback loop that influences growth
GH released by pit. —-> acts on hepatocytes to stimulate IGF-1 (insulin dependent) —-> IGF-1 inhibits GH
Why is GH stimulation of IGF-1 insulin dependent?
because you don’t want growth to occur in times of starvation
Which hormone is responsible for maintaining lean body mass?
GH
What does IGF-1 do?
mimics insulin in muscle but NOT in liver and adipose due to lack of IGF-1 receptors
When in life is IGF-1 the highest?
puberty
What is the primary job of GH?
decrease adiposity (mobilize glucose in the blood - antagonist to what insulin is doing)
increases lipolysis and decreases glucose uptake in fat cells
GH ________ (increases/decreases) adiposity and __________ lean body mass
decreases (promotes lipolysis)
increases (promotes protein synthesis)
Is growing mediated by GH or IGF-1?
IGF-1!!! Does all the heavy lifting, just needs to be activated by GH
What does IGF-1 do?
increases organ size (kidney, pancreas, intestine, islets, skin, bone, heart, lung), function and linear growth
True or false: IGF-1 increases glucose uptake in the muscle
FALSE (decreases glucose uptake)
What 3 things promote GH decrease?
1) age
2) hyperglycemia
3) obesity
What 3 things promote GH increase?
1) stress (NE and ep)
2) exercise
3) starvation
What 2 conditions can GH excess lead to?
1) Gigantism (before closing of epiphyseal plate - long bones)
2) Acromegaly (thick bones, pituitary adenoma, enlarged facial features)
What does GH deficiency lead to?
dwarfism (chipdren)
What are the 2 types of dwarfism?
1) Laron Syndrome (no production of IGF-1, genetic defect in GH)
2) African pygmy (defect in GH receptor, some IGF-1 )
How do you treat dwarfism?
IGF-1
True or false: lactotropes are NOT part of endocrine axis
TRUE (no stimulating factor from hypothalamus)
Prolactin is tonically inhibited by ________
dopamine
Is prolactin bound to hormone binding protein?
NO, short half life (20 mins)
When is prolactin produced?
in response to suckling (stimulus-secretion reflex)
Prolactin is a very potent inhibitor of _______
GnRH
Prolactin is in the same family as ____
GH
What do prolactinomas lead to?
galactorrhea (milk production/discharge from breast)
reproductive dysfunction because prolactin inhibits GnRH
What does prolactin deficiency lead to?
Sheehan’s syndrome (occurs as result of excessive blood loss/shock during childbirth)
What happens to GH levels during insulin-induced hypoglycemia?
INCREASE
What happens to GH levels as IGF-1 is administered?
DECREASE
