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GHRELIN The next Anabolic
GHRELIN 101
Ghrelin: much more than a natural growth hormone secretagogue.
Ghrelin, a 28 amino acid acylated peptide predominantly produced by the stomach, displays strong growth hormone-releasing activity mediated by the hypothalamus-pituitary GH secretagogue receptors that were found to be specific for a family of synthetic, orally active GH secretagogues. The discovery of ghrelin brings us to a new understanding of the regulation of GH secretion. However, ghrelin is much more than simply a natural GH secretagogue. It also acts on other central and peripheral receptors and exhibits other actions, including stimulation of lactotroph and corticotroph secretion, orexigenic, influences gastroenteropancreatic functions, and has metabolic, cardiovascular and antiproliferative effects.
Interrelationship between the novel peptide ghrelin and somatostatin/growth hormone-releasing hormone in regulation of pulsatile growth hormone secretion.
GH is an anabolic hormone that is essential for normal linear growth and has important metabolic effects throughout life. The ultradian rhythm of GH secretion is generated by the intricate patterned release of two hypothalamic hormones, somatostatin (SRIF) and GHRH, acting both at the level of the pituitary gland and within the central nervous system. The recent discovery of ghrelin, a novel GH-releasing peptide identified as the endogenous ligand for the GH secretagogue receptor and shown to induce a positive energy balance, suggests the existence of an additional neuroendocrine pathway for GH control. To further understand how ghrelin interacts with the classical GHRH/SRIF neuronal system in GH regulation, we used a combined physiological and histochemical approach. Our physiological studies of the effects of ghrelin on spontaneous pulsatile GH secretion in conscious, free-moving male rats demonstrate that
1) ghrelin, administered either systemically or centrally, exerts potent, time-dependent GH-releasing activity under physiological conditions;
2) ghrelin is a functional antagonist of SRIF, but its GH-releasing activity at the pituitary level is not dependent on inhibiting endogenous SRIF release;
3) SRIF antagonizes the action of ghrelin at the level of the pituitary gland
4) the GH response to ghrelin in vivo requires an intact endogenous GHRH system. Our dual chromogenic and autoradiographic in situ hybridization experiments provide anatomical evidence that ghrelin may directly modulate GHRH mRNA- and neuropeptide Y mRNA-containing neurons in the hypothalamic arcuate nucleus, but that SRIF mRNA-expressing cells are not major direct targets for ghrelin.
Together, these findings support the idea that ghrelin may be a critical hormonal signal of nutritional status to the GH neuroendocrine axis serving to integrate energy balance and the growth process.
1)Isr Med Assoc J 2002 Aug;4(8):607-13 (ISSN: 1565-1088)
Broglio F; Arvat E; Benso A; Gottero C; Prodam F; Granata R; Papotti M; Muccioli G; Deghenghi R; Ghigo E
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy
2)Endocrinology 2003 Mar;144(3):967-74 (ISSN: 0013-7227)
Tannenbaum GS; Epelbaum J; Bowers CY
Department of Pediatrics, McGill University and the Neuropeptide Physiology Laboratory, McGill University-Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada H3H 1P3. gloria.tannembaum@mcgill.ca.
Ghrelin may prove to be a most interesting hormone and a true anabolic hormone, but it will take some time to sort it all out. One recent study called "Ghrelin---not just another stomach hormone" (Wang G, Lee HM, Englander E, Greeley GH." Regul Pept 2002 May 15;105(2):75-81) suggests Ghrelin has effects on GH. Below is the abstract:
"Growth hormone (GH) secretagogues (GHSs) are non-natural, synthetic substances that stimulate GH secretion via a G-protein-coupled receptor called the GHS-receptor (GHS-R). The natural ligand for the GHS-R has been identified recently; it is called ghrelin. Ghrelin and its receptor show a widespread distribution in the body; the greatest expression of ghrelin is in stomach endocrine cells. Administration of exogenous ghrelin has been shown to stimulate pituitary GH secretion, appetite, body growth and fat deposition.
Ghrelin was probably designed to be a major anabolic hormone. Ghrelin also exerts several other activities in the stomach. The findings that ghrelin is produced in mucosal endocrine cells of the stomach and intestine, and that ghrelin is measurable in the general circulation indicate its hormonal nature. A maximal expression of ghrelin in the stomach suggests that there is a gastrointestinal hypothalamic-pituitary axis that influences GH secretion, body growth and appetite that is responsive to nutritional and caloric intakes."
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