Abstract
Growth hormone (GH) is essential for normal growth and development. It has been recognized that the synthesis and secretion of GH are regulated by hypothalamic growth hormone-releasing hormone (GHRH) and somatostatin (SS) . Complementary DNAs for these hormones and their receptors have recently been cloned, and the regulation of their expression has been studied extensively. Receptors for both GHRH and SS are associated with G proteins that regulate adenylate-cyclase activity, and thereby GH synthesis and secretion. In addition, a group of peptides (GH-releasing peptides [GHRPs]) with potent GH-stimulating activity has been synthesized. These peptides appear to stimulate GH secretion via protein kinase C (PKC). The recently identified GHRP receptors will stimulate the search for endogenous GHRPs that may be useful in the treatment of patients with some types of GH deficiency. In addition, the transcription factor pit-1 has been shown to be necessary for somatotroph development and GH synthesis. GH has a number of effects on carbohydrate, lipid, protein and electrolyte metabolism. These effects are mediated by GH receptors that are associated with the tyrosine kinase JAK 2 kinase. PKC is also utilized in GH-signalling. The extracellular domain of GH receptors (GH-binding protein [GHBP]) is detected in human serum. The growth-promoting action of GH is mediated mainly insulin-like growth factor I (IGF- I). IGF- I stimulates the growth and maturation of a number of cell types. IGF- I and its receptors are also involved in the growth of cancerous cells. It has been proposed that IGF-II is responsible for the hypoglycemia frequently associated with non-islet cell tumors. IGF- I and -II are complexed with IGF-binding proteins (IGFBPs) in the circulation. At least 6 species of IGFBP have been identified, but their physiological roles are as yet largely unknown.
