| Growth hormone-releasing hormone (GHRH) and somatostatin
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| HORMONE REPLACEMENT THERAPY (HRT) |
| Women normally reach menopause at 45-55 years of age. The absence of ovarian follicles leads to an absence of estrogen and inhibin secretion resulting in a marked rise in pituitary FSH. There are vasomotor symptoms of estrogen deficiency (flushing) associated with menopause. Long-term postmenopausal estrogen deficiency is known to increase the rate of bone loss, leading to osteoporosis, and also alters lipoprotein metabolism in a way that increases the risk of cardiovascular disease. |
| HRT with an estrogen preparation was standard practice in most developed countries both to relieve the acute symptoms and to provide prophylaxis against the long-term risks. However, recent studies have shown that HRT increases a woman's risk for breast cancer, cardiovascular disease, stroke, and pulmonary embolism. Although HRT did have a modest effect on preventing osteoporosis, there are newer drugs, the bisphosphonates, that are just as effective. The current recommendations are that HRT should only be used as short-term therapy for vasomotor symptoms that do not respond to other treatment. |
| GHRH is a 44-amino-acid peptide belonging to the secretin-vasointestinal peptide-glucagon family of hormones, and is synthesized as part of a 108-amino-acid prohormone. Immunohistochemical studies have located GHRH in the arcuate and ventromedial nuclei of the hypothalamus and in the median eminence. GHRH binds to its receptor on the pituitary somatotroph cell and triggers both the adeny
late cyclase and intracellular calcium-calmodulin systems to stimulate GH transcription and secretion from the anterior pituitary. Negative feedback from GH and IGF-I results in both a decrease in GHRH synthesis and secretion and an increase in somatostatin synthesis and secretion.
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Somatostatin is found in two forms with 14 and 28 amino acids , both of which are produced from the same 116-amino-acid gene product. Somatostatin and its receptors are found throughout the brain and also in other organs, notably the gut. Binding of somatostatin to its receptor is coupled to adenylate cyclase by an inhibitory guanine nucleotide-binding protein, resulting in a decrease in intracellular cAMP. In the context of growth, somatostatin inhibits the secretion of GH. GHRH and somatostatin are released in separate bursts to provide a very fine level of control of GH release. Somatostatin also inhibits basal and stimulated TSH release. Long-acting analogs of somatostatin are effective in the management of GH excess and tumors secreting a wide range of other hormones including TSH, insulin, and glucagon.
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