Ghrelin, an endogenous growth hormone secretagogue with diverse endocrine and nonendocrine effects

Abstract

Circulating ghrelin, the natural ligand of GHS-R 1a, is synthesized primarily in the stomach in mammals. The distribution of these receptors is consistent with the role of ghrelin in promoting secretion of GH; receptors are highly expressed in the hypothalamus and pituitary gland and are also distributed in other central and peripheral tissue sites. In addition to strong GH-releasing activity, ghrelin has other actions, including stimulation of lactotroph and corticotroph function, stimulation of appetite, regulation of energy homeostasis, stimulation of gastric motility and gastric acid secretion, regulation of insulin secretion and glucose metabolism, cardiovascular effects, and antiproliferative activity. These properties make ghrelin a candidate for future diagnostic and clinical applications. In mammals, secretion of GH from the adenohypophysis is regulated by 2 hypothalamic hormones with antagonistic actions: a stimulatory GHRH that is produced in the arcuate nucleus and an inhibitory hormone, somatostatin, synthesized in the paraventricular nucleus. 1 Both hormones are transported from the hypothalamus to target cells in the pituitary gland via the hypothalamo-hypophyseal portal system in the median eminence. Alternation in secretion of GHRH and somatostatin is responsible for the pulsatile pattern of GH release. 2,3 Measurement of GHRH and somatostatin in hypophyseal-portal blood in humans and other animals reveals that the episodic pattern of GHRH and somatostatin secretion does not fully account for all pulses of GH secretion. 4 The amplitude and frequency of GH secretory pulses are regulated by a complex array of external and internal stimuli, including body composition, age, sleep, gender, disease status, menstrual cycle phase, genetic background, and nutritional status. 5–7