Neuroendocrine control of growth hormone secretion

The secretion of growth hormone (GH) is regulated through a complex neuroen docrine control system, especially by the functional interplay of two hypot halamic hypophysiotropic hormones, GH-releasing hormone (GHRH) and somatost atin (SS), exerting stimulatory and inhibitory influences, respectively, on the somatotrope. The two hypothalamic neurohormones are subject to modulat ion by a host of neurotransmitters, especially the noradrenergic and cholin ergic ones and other hypothalamic neuropeptides, and are the final mediator s of metabolic, endocrine, neural, and immune influences for the secretion of GH. Since the identification of the GHRH peptide, recombinant DNA proced ures have been used to characterize the corresponding cDNA and to clone GHR H receptor isoforms in rodent and human pituitaries. Parallel to research i nto the effects of SS and its analogs on endocrine and exocrine secretions, investigations into their mechanism of action have led to the discovery of five separate SS receptor genes encoding a family of G protein-coupled SS receptors, which are widely expressed in the pituitary, brain, and the peri phery, and to the synthesis of analogs with subtype specificity. Better und erstanding of the function of GHRH, SS, and their receptors and, hence, of neural regulation of GH secretion in health and disease has been achieved w ith the discovery of a new class of fairly specific, orally active, small p eptides and their congeners, the GH-releasing peptides, acting on specific, ubiquitous seven-transmembrane domain receptors, whose natural ligands are not yet known.