Monday, August 17, 2009

Ghrelins and Associated Peptides

Definition
Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor (GHSR), which is synthesized principally in the stomach and is released in response to acute and chronic changes in nutritional state 1.

Related peptides
The ghrelin gene encodes a precursor protein, preproghrelin. Alternative mRNA splicing and/or proteolytic processing derives ghrelin and other potentially active peptides. The peptide obestatin is derived from the C-terminal region of preproghrelin and has direct effects on cell proliferation2. The ligand des-Gln14-ghrelin, a 27-amino acid peptide with an n-octanoyl modification at Ser3, is identical to ghrelin except for the deletion of one glutamine, and is produced through alternative splicing of the rat ghrelin gene. Des-Gln14-ghrelin has the same potency as ghrelin. On the other hand, the unmodified, des-n-octanoyl form of ghrelin (desacyl ghrelin) has no effect on the elevation of intracellular Ca2+ and GH secretion1. Other peptide hormones (i.e., motilin, TRH, PACAP, GnRH, leptin, FMRF amide, galanin, NPY, NPW) from gut, brain and other tissues also play a role in modulating GH secretion in livestock and lower vertebrate species 3.

Discovery
The discovery of ghrelin was reported by Masayasu Kojima and colleagues in 1999 4.

Structural characteristics
Ghrelin is synthesized as a preprohormone (13kDa), and then proteolytically processed to yield a 28 amino acid peptide (3kDa) with an n-octanoyl modification at its third serine residue, which is essential for its biological activity5.

Mechanism of action
The ghrelin receptor was known well before ghrelin was discovered. Cells within the anterior pituitary bear a growth hormone secretagoue receptor (GHS-R). Ghrelin bind to the GHS-R and stimulates the release of the growth hormone (GH).

Functions
Ghrelin potently induces GH release both in rats and humans. Ghrelin is primarily produced in distinct endocrine cells in the stomach. Ghrelin-producing neurons are also present in the hypothalamic arcuate nucleus, a region that regulates GH release and food intake. Ghrelin is also involved in the stimulation of feeding and the regulation of energy metabolism5.

References
1.Hosoda H, Kojima M, Kangawa K (2002). Ghrelin and the Regulation of Food Intake and Energy Balance. Molecular Interventions, 2(8):494-503.
2.Seim I, Amorim L, Walpole C, Carter S, Chopin LK, Herington AC (2009). Ghrelin gene-related peptides: multi-functional endocrine/autocrine modulators in health and disease. Clin Exp Pharmacol Physiol .
3.Anderson LL, Jeftinija S, Scanes CG, Stromer MH, Lee JS, Jeftinija K, Glavaski-Joksimovic A. (2005). Physiology of ghrelin and related peptides. Domestic Animal Endocrinology, 29(1):111-144.
4.Book: Ghrelin. Chapter 2: Discovery of Ghrelin, an Endogenous Ligand for the Growth-Hormone Secret Agogue Receptor. By Masayasu Kojima, Hiroshi Hosoda, Hiroyuki Kaiya and Kenji Kangawa.
5.Kangawa K, Kojima M, Hosoda H (2004). Ghrelin: discovery and physiological significance. Nippon Rinsho. 62 (9):317-323.

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