The physiology and potential clinical applications of ghrelin, a novel peptide hormone

Ghrelln, a peptide hormone originally Identified as the endogenous ligand of the growth hormone secretagogue receptor, Is secreted primarily from the stomach and secondarily from the small Intestine and colon. Ghrelln may also be expressed In the pancreatic islets, hypothalamus, pituitary, and several tissues In the periphery. The growth hormone secretagogue receptor Is widely expressed, suggesting diverse physiologic roles for ghrelin. A growing body of evidence suggests that, in addition to Its predictable effect on growth hormone secretion, ghrelin has an Important role In the short-term regulation of appetite and the long-term regulation of energy balance and glucose homeostasis. Recent studies have Implicated ghrelin In the regulation of gastrointestinal, cardiovascular, and Immune function and have suggested a role for ghrelin In bone physiology. The Identification of obestatin, a novel peptide hormone derived from the same gene as ghrelin, has recently added further complexity to ghrelin physiology. Obestatin appears to have actions opposite of ghrelin on energy homeostasis and gastrointestinal function. Despite the rapid progress, many questions remain unanswered, Including the regulation of ghrelin and obestatin secretion, the downstream pathways that mediate their effects, and their precise physiologic endocrine and paracrine roles. This review presents data on ghrelin structure, expression, and function, with emphasis placed on human studies, highlighting areas that require future Investigation and providing speculation about potential clinical applications of ghrelin agonists or antagonists.