ANAT 322 Lecture Notes - Lecture 5: Somatostatin Receptor, Stat5B, Excitatory Synapse
7 Jun 2018
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ANAT 322 Winter 2017
Lectures
Lecture 5:
→ A third player in GH regulation: Ghrelin and the GHS receptor
2. There has been a new player discovered in the regulation of GH, a third hormone called ghrelin.
3. The receptors was discovered before the hormone Ghrelin and is called the growth hormone
secretagogue receptors (GHS).
Earlier in the days, there were people with short stature that were perceived as having a real disorder
and researchers developed medication called growth hormone secretagogue. Secretagogues is a drug
that will promote or induce the secretion of something. When validating these drugs, they discovered
the receptors in which they act and gave the receptors this name since there was not known
endogenous ligand in the body for the receptor.
They increase intracellular Ca2+ levels and also increase production of GH receptors. It is not as
autonomous in its action as GHRH and SS in that it requires an intact hypothalamo-pituitary axis so it
does not work in people with malfunctions in that hormonal signaling.
4. They were able to find an endogenous substance for the receptor called ghrelin.
There is an octanoid acid group that can bind to plasma membrane and is abundant in the stomach.
The release of the substance is under control of the state of filling of the stomach and whether we are
hungry or not. It is concentrated also in the arcuate nucleus where we would find GHRH neurons.
6. Effects of Ghrelin at the pituitary level:
1. It couples via G-alpha (q) that results in activation of phospholipase C, another second messenger
enzyme located at the plasma membrane.
2. This will result in the hydrolysis of phosphatidylinositol 4,5-biphosphate (PIP2) into IP3 and
diacylglycerol (DAG).
3. This will then result in activation of protein kinase C (PKC) that will inhibit inwardly rectifying K+
channels and repolarize the plasma membrane potential. That means that when these K+ channels are
inhibited, it is easier for substances to depolarize the cell which causes Ca2+ influx and promotes
secretion. This is a way of action for ghrelin to promote release so that depolarization leads to Ca2+
influx through plasma membrane Ca2+ channels that leads to secretion.
4. The IP3 which is the actual second messenger will also activate receptors on the ER which is an
intracellular Ca2+ channels and this will also release Ca2+ but this is slower than effect on the plasma
membrane.
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ANAT 322 Winter 2017
Lectures
7. Ghrelin through its secretion in the stomach and bloodstream it can lead to the somatotropes in the
pituitary gland and affect them there. As well as through the Ghrelin neurons in the arcuate nucleus that
can stimulate GHRH neurons and reinforce that effects.
→ Clinical Aspects of GH Regulation
9. The big portion of the GH field in medicine relies on the question if there is such a thing as normal
growth and to what extend is growth governed by environmental influences or genetic influences.
11. Pediatric growth curve in which around the age of 18 our growth in body height ends.
Data accuulated fro the Motreal Childre’s hospital i which there is a edia of 1.77 c (thick
blue line) for boys and there is a wide spectrum in the population.
There are instances where children do not fit in that curve that has to do with abnormal growth
hormone secretion.
12. GH deficiency or loss of responsiveness to GH can be genetic and is called familial short stature or
growth hormone deficiency.
There can be overgrowth and if it happens during childhood it is called gigantism but if it afflicts
adults it results in acromegaly which is really dangerous.
13. These are five siblings not too far apart in age and two are relatively tall but within normal curve and
three of the siblings are short which is referred to as severe short stature. The most common reason is
GH deficiency but there can be more reasons.
If it is familial and based on an identifiable mutation in the GH locus it accounts for 1% of the cases.
GH receptors defects accounts for 10% so there is higher incidence.
There can also be genetic causes in defects in the GH receptor or within the signaling pathway of the
GH receptor but that is rare.
All effects of GH on longitudinal growth are mediated by IGF-I receptors so this can also be caused by
loss of function mutation in this but it is rare.
14. More cases of short stature in which the cause is not known are called idiopathic short stature.
In in vitro test and biopsies the cells respond to GH, however, in a small subset there are elevated GH
in plasma but low IGF-I levels suggesting something wrong in the tissue that makes it resistant.
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Earlier in the days, there were people with short stature that were perceived as having a real disorder and researchers developed medication called growth hormone secretagogue. Secretagogues is a drug that will promote or induce the secretion of something. When validating these drugs, they discovered the receptors in which they act and gave the receptors this name since there was not known endogenous ligand in the body for the receptor. They increase intracellular ca2+ levels and also increase production of gh receptors. There is an octanoid acid group that can bind to plasma membrane and is abundant in the stomach. The release of the substance is under control of the state of filling of the stomach and whether we are hungry or not. It is concentrated also in the arcuate nucleus where we would find ghrh neurons: effects of ghrelin at the pituitary level:
