Neuroendocrine Regulation of Growth Hormone Secretion

Abstract

This article reviews the main findings that emerged in the intervening years since the previous volume on hormonal control of growth in the section on the endocrine system of the Handbook of Physiology concerning the intra- and extrahypothalamic neuronal networks connecting growth hormone releasing hormone (GHRH) and somatostatin hypophysiotropic neurons and the integration between regulators of food intake/metabolism and GH release. Among these findings, the discovery of ghrelin still raises many unanswered questions. One important event was the application of deconvolution analysis to the pulsatile patterns of GH secretion in different mammalian species, including Man, according to gender, hormonal environment and ageing. Concerning this last phenomenon, a great body of evidence now supports the role of an attenuation of the GHRH/GH/Insulin-like growth factor-1 (IGF-1) axis in the control of mammalian aging.

Clonidine Plus GHRH Administration for Diagnosing Growth Hormone Deficiency in Children

“…Interestingly, in that Table 1 it could be seen that none of the children of the subgroup 1 responded to the Insulin-induced hypoglycaemia, a test considered to be the "gold standard test", while four of them showed a positive response to CLO + GHRH, and even in two of these patients a response to GHRH given alone could be observed. This is quite surprising since it is well known that hypoglycaemia induces an adrenergic response; in fact catecholamines form part of the group of counter regulatory hormones that oppose the action of insulin, and they also act by blocking hypothalamic somatostatin release [18], then allowing the endogenous GHRH to be released [10,11]. Therefore a positive response should be observed in these cases, as it happened in four of them when they were tested with CLO + GHRH or in three of these children after being stimulated with propranolol plus exercise ( Table 1).…”

“…Another possibility, such as the lack of hypothalamic GHRH production, has to be discarded since in this subgroup 1 there was a positive response to propranolol plus exercise in three cases, and in two patients challenged with GHRH alone (Table 1). Since GHRH induces the pituitary synthesis of GH [10,11], no response to exogenous GHRH administration should be observed in these two patients given that no pituitary stores of GH could exist. These divergences among the different tests carried out were also observed in the other subgroups of children, with the unique exception of CLO+GHRH test for which a positive GH response was observed in all cases ( Table 1).…”

“…Among them, the intricate relationships between auto/paracrine effects of GH, SS and GHRH on its own secretion, the pituitary production of IGF-I, the role of the gastric hormone Ghrelin, or the release of leptin by adipocytes, nutritional conditions, stress, etc. [11]. In addition, many recent data indicate that the aging-suppressor gene Klotho is a direct regulator of GH secretion [35].…”

“…Therefore, only when there is a physiological interruption of SS secretion, GHRH may be released and act on the pituitary synthesis and release of GH [10,11].…”

“…Hypothalamic somatostatin release is negatively controlled by adrenergic and cholinergic pathways [10,11]. Therefore, the administration of alpha2-adrenergic agonists such as clonidine (CLO) will reduce, or impede, somatostatin secretion, allowing pituitary GH release to be enhanced [18][19][20].…”