CLINICAL CASES
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GHRH: Growth hormone-releasing hormone; a peptide synthesized and
secreted by the hypothalamus. GHRH stimulates the synthesis and
secretion of GH.
IGF-1: Insulin-like growth factor-1, also called somatomedin C; a 70-amino
acid peptide that shares structural homology with proinsulin. IGF-1 is
synthesized and released by the liver in response to growth hormone
binding to receptors on the hepatocyte.
JAK2: Janus kinase 2; an enzyme that will phosphorylate tyrosine residues
on target proteins. JAK2 is bound to the growth hormone receptor but is
inactive until the receptor binds the hormone. When hormone binds the
receptor, it triggers dimerization and activates JAK2.
Somatotropin: Growth hormone; a 191-amino acid polypeptide hormone
that is synthesized and secreted from the somatotroph cells of the ante-
rior pituitary. It acts primarily on hepatocytes, although muscle and adi-
pose cells also have receptors for growth hormone.
D ISC U SSIO N
Growth hormone (somatotropin) is a polypeptide synthesized and secreted
by somatotrophs in the anterior pituitary. Growth hormone synthesis and
secretion is stimulated by the hypothalamic peptide growth hormone-
releasing hormone (GHRH). Somatostatin, a polypeptide produced by sev-
eral tissues including the hypothalamus, opposes GHRH stimulation of
growth hormone release. High levels of insulin-like growth factor-1 (IGF-1)
directly suppress growth hormone production in somatotrophs and also act
indirectly by stimulating somatostatin release from the hypothalamus.
Furthermore, growth hormone itself directly feedback inhibits its synthesis in
the somatotroph and also inhibits GHRH production by the hypothalamus.
A potent stimulator of growth hormone release is ghrelin, a polypeptide hormone
secreted by the stomach that acts directly on somatotrophs. In general, many
environmental factors including stress, exercise, nutrition, and sleep influence cir-
culating levels of growth hormone. The overall effect is a pulsatile pattern of
growth hormone release reaching a maximum in children and young adults
shortly after the onset of deep sleep. Levels of growth hormone fluctuate dramat-
ically and are suppressed in normal individuals after oral glucose administration.
Growth hormone plays a major role in cell proliferation and in regulat-
ing protein, lipid, and carbohydrate metabolism. It stimulates protein syn-
thesis and the accompanying amino acid uptake in many tissues. In adipocytes,
it increases fat utilization by stimulating triglyceride breakdown and oxidation.
It opposes effects of insulin by suppressing its ability to stimulate glucose
uptake and by stimulating gluconeogenesis. Interestingly, injection of growth
hormone stimulates insulin secretion, leading to hyperinsulinemia.
In most of these examples, growth hormone acts at two levels. Growth hor-
mone acts directly by binding its receptors in the plasma membrane of target
cells to influence cell proliferation and metabolism. Binding of growth hormone
to its receptor triggers receptor dimerization. In the absence of bound hormone,
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