Ghrelin is a 28 amino acid peptide that is the natural ligand for the growth hormone secretagogue (GHS) receptor [1,2]. Based on its structure, it is a member of the motilin family of peptides. When administered peripherally or into the central nervous system, ghrelin stimulates secretion of growth hormone, increases food intake, and produces weight gain [3,4].
Ghrelin, which is produced by the stomach, increases during periods of fasting or under conditions associated with negative energy balance such as starvation or anorexia. In contrast, ghrelin levels are low after eating or with hyperglycemia, and in obesity. Accumulating evidence indicates that ghrelin plays a central role in the neurohormonal regulation of food intake and energy homeostasis.
This topic review will provide an overview on the biology of ghrelin. Related subjects are discussed separately. (See "Pathogenesis of obesity" and "Physiology of leptin" and "Drug therapy of obesity".)
Ghrelin was discovered in 1999 when it was noted that tissue extracts from the rat stomach activated the GHS receptor . It has since been recognized that the stomach is the richest source of ghrelin. Over 90 percent of the body's ghrelin is in the stomach and duodenum. Lower amounts are found in the pancreas, pituitary, kidney, and placenta. A limited region of the arcuate nucleus of the hypothalamus contains small amounts of ghrelin.
Ghrelin is most abundant in the gastric fundus where it is produced in oxyntic glands by distinctive endocrine cells known as P/D1 cells [5,6]. Ghrelin-containing cells are of two types: