Growth Hormone Secretion and Regulation

PHARMACOLOGY

Growth Hormone Secretion and Regulation

Growth hormone is secreted from somatotrophs in the anterior pituitary. Multiple feedback loops are present in normal regulation of hGH secretion (Casanueva, 1992; Giustina and Veldhuis 1998) (Fig. 3). Growth hormone release from the pituitary is regulated by a “short loop” of two coupled hypothalamic peptides—a stimulatory peptide,

growth hormone releasing hormone (GHRH) and an inhibitory peptide, somatostatin. GHRH and somatostatin are, in turn, regulated by neuronal input to the hypothalamus and the GH secretagogue, ghrelin (Kojima et al., 2001). There is possibly also an “ultrashort loop” in which hGH release is feedback regulated by growth hormone receptors present on the somatotrophs of the pituitary them-selves. Growth hormone secretion is also regulated by a “long loop” of peripheral signals including insulin-like growth factor (IGF-1) and other modulators.

Growth hormone secretion changes during human development, with the highest production rates observed during gestation and puberty (Brook and Hindmarsh 1992; Guistina and Veldhuis, 1998). Growth hormone production de-clines approximately 10 to 15% each decade from age 20 to 70 years. Endogenous hGH secretion also varies with sex, nutritional status, obesity, physical activity, and in a variety of disease states. Endogenous hGH is secreted in periodic bursts over a 24 hour period with great variability in burst frequency, amplitude and duration. There is little detectable hGH released from the pituitary between bursts. The highest endogenous hGH serum con-centrations of 10 to 30 ng/mL usually occur at night when the secretory bursts are largest and most frequent.