Growth Hormone and Somatomedin Flashcards
which hypothalamic hormones regulate the pulsatile secretion of GH
GHRH
somatostatin (also called somatotropin release-inhibiting factor, SRIF)
after GHRH interacts with its membrane receptor…
increases cAMP and Ca2+ levels in the cell
negative feedback loop on GH secretion
insulin-like growth factor-1 (IGF-1) that is released from liver and other tissues….
inhibits release of GH from pituitary gland
What stimulates the secretion of GHRH from the hypothalamus
sleep, stress, amino acid rich meal
leads to increase GH from pituitary gland
short term vs long term effects of GHRH on the somatotrophs
short = increased release of stored GH
long = increased transcription of the GH gene
–> activates the pituitary gland transcription factor (Pit1)
Thyroid hormone and cortisol effect on GH
synergistically enhance transcription of GH gene
what stimulates release of somatostatin from the hypothalamus
somatomedin (IGF) and GH
leads to decreased release of GH from pituitary gland
somatomedin regulation on GH release
(+) somatostatin release from hypothalamus –> less GH
and
directly (-) GH release at pituitary gland by interacting with receptor and decreasing cAMP and Cs2+
on the balance, GH can partially be considered what kind of hormone
diabetogenic
effects downstream of high protein intake…
(+) GH and (+) insulin –> caloric storage (+/-)
(+) somatomedin –> (+) protein synthesis, (+) growth
effects downstream of carbohydrate intake…
(-) GH with (+) insulin –> (+) caloric storage
(+/-) somatomedin –> (+/-) protein synthesis and growth
effects downstream of fasting
(+) GH with (-) insulin –> caloric mobilization
(-) somatomedin –> (-) protein synthesis and growth
effects of GH on the liver
increase in the following…
- RNA and protein synthesis
- gluconeogenesis
- synthesis and secretion of IGFBPs and IGFs
effects of GH and IGFs on muscle
(-) glucose uptake
(+) amino acid uptake
(+) protein synthesis
(+) lean body mass
effects of GH on adipose tissue
(-) glucose uptake
(+) lipolysis
(-) adiposity
***IGFs do not effect adipose tissue like they do muscle
GH and IGF effects on extrahepatic tissues
increases in the following
protein, RNA, and DNA synthesis
cell and organ size
organ function
GH and IGF effects on chondrocytes
increases in the following…
amino acid uptake RNA/DNA/protein synthesis collagen chondroitin sulfate cell size and number linear growth
fetal GH detection
detectable in the fetal serum
concentration increases rapidly and peaks at 100-150ug/L at about 20th week
GH concentration in premature babies
higher than normal babies
levels decrease to about 30 and continue to fall during the early postnatal months
somatostatin effect on the function of GHRH
blocks GHRH stimulation on the pituitary gland by a non competitive means
interacts with own membrane receptor to decrease cAMP and Ca2+
also lowers frequency and amplitude of GHRH release from hypothalamus
sharp drop in glucose and fFAs –>
increase GH
obesity and GH
reduces GH responses to all stimuli
including GHRH
nocturnal surge of GH
1-2 hours after onset of deep sleep (not REM)
REM lowers GH
mechanism of GH action
- attaches to 2 docking sites on receptor
- receptor dimerizes
- intracellular domains then dock and activate JAK-STAT tyrosine kinase pathway
- these kinases phosphorylate STAT transcription factor proteins
- which activate GH-dependent gene transcription and expression –> modulation of IGFs, IGFBPs and other molecules expression
what organ makes most of the IGFs
liver
circulation of IGFs
bound to a number of large binding proteins that regulate their availability to tissues
GH deficient patients level of IGFs
lowered
especially IGF-1
what stimulates IGF production during fetal growth
a GH variant present in the placenta
the IGF-2 and its receptor are expressed very early in fetal development
the progression of pubertal growth correlates with the plasma increases in what
IGF-1
IGF and GH levels in fasting state
GH is elevated but IGFs are lowered
therefore,
must be other factors regulating IGF production…
soooooo
high GH levels probably result from a negative feedback mechanism caused by low IGFs
cortisol and estrogens on IGF production
lower it
any hormones that antagonizes GH action will lower IGFs too
GH effect on chondrocytes
stimulates differentiation of prechondrocytes into chondrocytes which then secrete IGF-1
which stimulates clonal expansion and maturation of chondrocytes
insulin antagonistic effect of GH helpes prevent what
hypoglycemia
insulin and GH and IGF levels after fasting
insulin falls
GH rises
but IGF still fall
why is GH increase during fasting good?
contributes to enhanced lipolysis and decreases peripheral tissue glucose use
Prolactin struture compared to GH
very much homologous except for extra 3rd disulfide bonded loop
how is prolactin made
made as a preprohormone
signal peptide is cleaved in ER membrane
temporarily N-glycosylated in ER then taken off in Golgi
secretion of prolactin regulation
inhibited by prolactin inhibitory factors (PIFs) from hypothalamus –> primarily dopamine
others include somatostatin and alternatively spliced GnRH
Thyroid releasing hormone (TRH) is a major stimulator of prolactin
