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Scientifica  2013 

Structure and Physiological Actions of Ghrelin

DOI: 10.1155/2013/518909

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Abstract:

Ghrelin is a gastric peptide hormone, discovered as being the endogenous ligand of growth hormone secretagogue receptor. Ghrelin is a 28 amino acid peptide presenting a unique n-octanoylation modification on its serine in position 3, catalyzed by ghrelin O-acyl transferase. Ghrelin is mainly produced by a subset of stomach cells and also by the hypothalamus, the pituitary, and other tissues. Transcriptional, translational, and posttranslational processes generate ghrelin and ghrelin-related peptides. Homo- and heterodimers of growth hormone secretagogue receptor, and as yet unidentified receptors, are assumed to mediate the biological effects of acyl ghrelin and desacyl ghrelin, respectively. Ghrelin exerts wide physiological actions throughout the body, including growth hormone secretion, appetite and food intake, gastric secretion and gastrointestinal motility, glucose homeostasis, cardiovascular functions, anti-inflammatory functions, reproductive functions, and bone formation. This review focuses on presenting the current understanding of ghrelin and growth hormone secretagogue receptor biology, as well as the main physiological effects of ghrelin. 1. Introduction Ghrelin is a unique 28 amino acid peptide containing an n-octanoyl group on the serine in position 3 that was purified from rat stomach in 1999 [1, 2]. Ghrelin is the only known peptide hormone modified by a fatty acid. Ghrelin is synthesized by the endocrine X/A-like cells of the fundus mucosa representing about 20% of gastric mucosal cells in humans [3–5]. Ghrelin is the natural ligand for the growth hormone secretagogue (GHS) receptor (GHS-R) cloned in 1996 [6]. Circulating ghrelin consists of more than 90% of desacyl ghrelin and less than 10% acyl ghrelin [7]. However, the acyl group of ghrelin is essential for its binding to GHS-R and the concomitant activation of the inositol triphosphates/calcium pathway [1, 2]. In addition to the stomach [1, 8], ghrelin is expressed in many tissues such as duodenum, jejunum, ileum, colon, lung, heart, pancreas, kidney, testis, pituitary, and hypothalamus [3, 9–13]. The major biological functions of ghrelin include the secretion of growth hormone, the stimulation of appetite and food intake, the modulation of gastric acid secretion and motility, and the modulation of the endocrine and exocrine pancreatic secretions. 2. From Ghrelin Gene to Ghrelin-Related Peptides 2.1. Transcriptional and Translational Mechanisms The human ghrelin gene is located on the short arm of chromosome 3 (3p25-26) and contains six exons (2 are noncoding) and 4 introns and

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