For some time now, the authors have been investigating the neuroendocrine events leading to increased growth hormone (GH) secretion following administration of GH secretagogues, including GH-releasing peptide (GHRP-6). It is now well established that these compounds act both at the pituitary (1-5) and within the central nervous system (CNS) (6,7). The recent cloning of the GHRP-6 receptor has paved the way for the localization of the receptors at both pituitary and hypothalamic sites (8).
In most species, GH is secreted in a highly pulsatile pattern that is believed to reflect a balanced alternation in the output of two neuroendocrine systems, the GH-releasing hormone (GHRH) neurons and the inhibitory somatostatin neurons. The effects of GH secretagogue administration on the pattern of GH secretion are complex and may be mediated, at least in part, by modification of the output ofthe central GHRH-somatostatin pulse generator. However, to date, no endogenous ligand for GH secretagogues has been
From: Human Growth Hormone: Research and Clinical Practice Edited by: R. G. Smith and M. O. Thorner © Humana Press Inc., Totowa, NJ
identified, and hence, it is not clear whether such a ligand participates in the normal physiological control of pulsatile GH secretion. In conscious male rats, a GHRP-6 infusion causes an initial GH peak followed by a sustained elevation of plasma GH concentrations during which pulses occur, but the normal three hourly pulsatile rhythm is disrupted (9). Similar responses have been observed in pigs infused with the nonpeptide secretagogue L-700,653 (10) and in guinea pigs infused with L-692,585 (11). Here we will review what is known about the central site and mechanism of action of the GH secretagogues to consider how an endogenous GH secretagogue ligand might influence the GHRH-somatostatin pulse generator network; and to consider the physiological circumstances in which such a ligand might be released will be reviewed.
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