Control of growth hormone (GH) release by GH secretagogues

Despite its long-term role in postnatal growth and metabolism, pituitary growth hormone (GH) is secreted in a short-term highly episodic pulsatile pattern in all species in which it has been examined. This pattern is tightly controlled by the interplay of GH-releasing hormone (GHRH) and somatostatin (SRIF), the primary hypothalamic factors that determine GH secretion from the somatotroph and which also regulate GH synthesis and secretory reserve. The discovery of a endogenous receptor for synthetic GH secretagogues (GHS)s that differ from GHRH implies the existence of at least one other endogenous GHS system, though the physiological role of the hypothetical GHS ligand remains unclear. The GH secretory pattern is sexually dimorphic with sex differences at many levels in the hypothalamo-pituitary somatotroph axis. Studies in transgenic animals have shown that GH output is also highly sensitive to feedback control by GH itself, as well as by insulin-like growth factor I. Peripheral responses to GH are markedly dependent on the pattern of GH exposure, which is further modified after secretion by interaction with GH binding proteins and with GH receptors, both also regulated by the pattern of GH exposure. Although the hypothalamic GH pulse generator is of central importance in the control of GH output, its origin, location and mechanisms remain to be elucidated.