Growth hormone is a 191-amino-acid peptide with two sulfhydryl bridges. Its structure closely resembles that of prolactin. In the past, medicinal GH was isolated from the pituitaries of human cadavers. However, this form of GH was found to be contaminated with prions that could cause Creutzfeldt-Jakob disease. For this reason, it is no longer used. Somatropin, the recombinant form of GH, has a 191-amino-acid sequence that is identical with the predominant native form of human GH.
B. Absorption, Metabolism, and Excretion
Circulating endogenous GH has a half-life of approximately 20 minutes and is predominantly cleared by the liver. Recombinant human GH (rhGH) is administered subcutaneously 6–7 times per week. Peak levels occur in 2–4 hours, and active blood levels persist for approximately 36 hours.
Growth hormone mediates its effects via cell surface receptors of the JAK/STAT cytokine receptor superfamily. The hormone has two distinct GH receptor binding sites. Dimerization of two GH receptors is stimulated by a single GH molecule and activates
TABLE 37–3 Diagnostic uses of thyroid-stimulating hormone and adrenocorticotropin.
signaling cascades mediated by receptor-associated JAK tyrosine kinases and STATs (see Chapter 2). The hormone has complex effects on growth, body composition, and carbohydrate, protein, and lipid metabolism. The growth-promoting effects are mediated principally, but not solely, through an increase in the production of IGF-I. Much of the circulating IGF-I is produced by the liver. Growth hormone also stimulates production of IGF-I in bone, cartilage, muscle, kidney, and other tissues, where it has autocrine or paracrine roles. It stimulates longitudinal bone growth until the epiphyseal plates fuse—near the end of puberty. In both children and adults, GH has anabolic effects in muscle and catabolic effects in adipose cells that shift the balance of body mass to an increase in muscle mass and a reduction in adiposity. The direct and indirect effects of GH on carbohydrate metabolism are mixed, in part because GH and IGF-I have opposite effects on insulin sensitivity. Growth hormone reduces insulin sensitivity, which results in mild hyperinsulinemia and increased blood glucose levels, whereas IGF-I has insulin-like effects on glucose transport. In patients who are unable to respond to growth hormone because of severe resistance (caused by GH receptor mutations, post-receptor signaling mutations, or GH antibodies), the administration of recombinant human IGF-I may cause hypoglycemia because of its insulin-like effects.
A. Growth Hormone Deficiency