Lecture 4 (71): Posterior Pituitary and HPL Axis Flashcards
Where are AVP and OXY released from?
POSTERIOR PITUITARY
- magnocellular neuron (hypothalamus)
- Neurhypophysial tract
- Posterior pituitary
What is the structure of AVP and OXY?
How are they transcribed?
What are their pro hormones composed of?
1.Nonapeptides
(9 amino acids)
- Transcribed as a preprohormone
- Prohormones:
AVP + neurophysin II,
OXY + neurophysin I
AVP:
Cell bodies located where? (2)
PVN has two types of cells: magnocellular and parvocellular. Only ______ neurons project to posterior pituitary.
Parvocellular PVN neurons that contain AVP project to _____and are important for regulating mood (anxiety)/stress.
AVP in magnocellular SON and PVN important for _____
Neurophysin is cleaved from the pro hormone when?
- paraventricular nucleus (PVN) and supraoptic nucleus (SON).
- magnocellular
- median eminence
- maintaining fluid balance.
- secretory granules during axonal transport.
What are the 2 main targets of AVP?
What is it MOST sensitive to?
- Kidney
- Vasculature (Mean Arterial BP)
- CN 9 and 10
OSMOLARITY
When below 285 mosm/mL = no AVP, above threshold STEEP INCREASE
- causes increased water reabsorption and vasoconstriction
What type of signaling does AVP use?
G protein
V1 = muscle
V2 = kidney
PLC IP3 calcium contracts muscle
What do V2 receptors in the kidney do when AVP is stimulated?
V2 receptors in the kidney
-phosphorylates aquaporin 2 channels (only in COLLECTING DUCTS OF KIDNEY)
inserts them into the membrane
allows for water reabsorption into the collecting ducts
What symptom is present in all Diabetets types?
What are the 2 main causes?
Excessive urine production
1.Decreased AVP release – most common defect
Hypothalamic or pituitary defect “central” due to trauma, cancer, or infectious disease.
- Decreased renal responsiveness to AVP
Genetic: X-linked mutation in AVP type-2 receptor – 90% males
Acquired: LITHIUM treatment, hypokalemia (more common)
AVP levels are normal responding to osmolarity
What is the function of OXYTOCIN? (2)
Is this positive or negative feedback?
What stops it?
OXYTOCIN stimulates
1. contraction of uterus 2. milk ejection (nothing to do with milk production though!)
- POSTIVE
- Birth or when suckling stops
OXYtocin acts similarly to AVP. How?
- Increase PLC and IP3
- MLCK activated by Ca-CaM
- Contraction of smooth muscle
How are GHRH and Somatostatin related?
stimulate the anterior pituitary SOMATOTROPHS
What are the 3 components of the HPL axis of GHRH and Somatostatin?
- Arcuate Nucleus
- Somatotrope
- Liver
What are the 3 targets of GH?
- Adipose tissue
- Liver
- Muscle
What is the structure of GHRH?
Where is it produced?
What does it stimulate?
44 amino acid peptide
Produced in the arcuate nucleus
Stimulates growth hormone (GH) from the anterior pituitary
What is the structure of Somatostatin?
What is its function?
What does it inhibit?
28 or 14 amino acid peptide (made in PVN of hypothalamus)
Inhibitor of GHRH at the level of the hypothalamus
Inhibits GH and TSH in pituitary
What are the 2 types of SS?
Where are they made?
SS28 – made by D cells in stomach and duodenum (Furin)
SS14 made in hypothalamus (PVN) and pancreatic delta cells (PC1/PC2).
SS14 and SS28 have identical amino termini
Somatostatin modulates GHRH pulsatility (decreased frequency) in ______.
Somatostatin inhibits GH release in _____.
- hypothalamus
- pituitary
-inhibits the PULSATILE FREQUENCY of GHRH AND the release of GHRH at the Posterior Pituitary
* NEEDS BOTH FUNCTION*
pulasitility important for downstream function
and to inhibit GH release
Which of the following have an inverse relationship?
- Somatostatin
- GH
- GHRH
Somatostatin & GHRH And GH
Somatotrope (Grown hormone) is pulsatile release, mostly when?
At night?
How does GH affect IGF-1? (insulin like growth factor)?
GH stimulates IGF-I production in the liver
What is the negative feedback of GH?
IGF-I mimics insulin in ____, but not _____ and adipose due to lack of receptors
- IGF-1
1. Muscle, liver
GH will not sitmulate IGF-1 in the liver in the absence of what?
INSULIN
- if you are starving and blood glucose levels are low, do NOT want to be growing
- GH maintains lean body mass - increases protein synthesis in muscle!
IGF-I mimics insulin in muscle, but not liver and adipose due to lack of receptors!!!!
they are direct targets of GH and there are no IGF – 1 receptors here
IGF-1 peaks when?
IGF1 peaks during puberty similar to growth hormone
defects with GH are associated with defect in IGF-1
- HIGHEST DURING PUBERTY
What are the direct affects of GH?
Indirect?
- Adipose tissue = increase lipolysis
- Liver = increase IGF’s
- Muscle
= DECREASE glucose uptake (more will be in the blood)
increase protein synthesis
INDIRCT: via IGF-1
- Increase cell size and number of kidney, pancreas, intestine, skin bone, DOES NOT DECREASE glucose uptake in the muscle (this is mediated by GH not IGF-1)
What 5 things stimulate GH?
4 Inhibit?
- GHRH
- DOpamine
- NE/E
- Amino acids
- THyroid Hormones
INHIBIT GH:
- SOmatostatin
- IGF-1
- GLucose (hyperglycemia)
- Free Fatty Acids (obesity)