Ghrelin: Structure and Function

Abstract

Small synthetic molecules called growth hormone secretagogues (GHSs) stimulate the release of growth hormone (GH) from the pituitary. They act through the GHS-R, a G protein-coupled receptor whose ligand has only been discovered recently. Using a reverse pharmacology paradigm with a stable cell line expressing GHS-R, we purified an endogenous ligand for GHS-R from rat stomach and named it “ghrelin,” after a word root (“ghre”) in Proto-Indo-European languages meaning “grow.” Ghrelin is a peptide hormone in which the third amino acid, usually a serine but in some species a threonine, is modified by a fatty acid; this modification is essential for ghrelin's activity. The discovery of ghrelin indicates that the release of GH from the pituitary might be regulated not only by hypothalamic GH-releasing hormone, but also by ghrelin derived from the stomach. In addition, ghrelin stimulates appetite by acting on the hypothalamic arcuate nucleus, a region known to control food intake. Ghrelin is orexigenic; it is secreted from the stomach and circulates in the bloodstream under fasting conditions, indicating that it transmits a hunger signal from the periphery to the central nervous system. Taking into account all these activities, ghrelin plays important roles for maintaining GH release and energy homeostasis in vertebrates.

Ghrelin in obesity and endocrine diseases

“…In addition, ghrelin is amongst the most powerful of the orexigenic peptides (Kojima & Kangawa, 2005). While most orexigenic peptides originate from the brain and are only active when injected into the brain, ghrelin is active even with peripheral administration leading to an increase in appetite in rodents and humans (Wren et al, 2001a;Wren et al, 2001b).…”

“…This post-translational modification is mediated by ghrelin O-acyltransferase (GOAT) (Yang et al, 2008) and is essential for GHS-R1a activation and the endocrine actions of ghrelin (Kojima & Kangawa, 2005). Consistent with its function, GOAT mRNA is primarily limited to the stomach; the main ghrelin-secreting tissue (Yang et al, 2008).…”

Ghrelin and its promoter variant associated with cardiac hypertrophy

“…2 Ghrelin 3 and its receptor 4 are synthesized and secreted also by human and mouse cardiomyocytes. Ghrelin may protect cardiomyocytes from apoptosis, probably by paracrine/autocrine actions.…”

Evaluation and Diagnostic Potential of Serum Ghrelin in Feline Hypersomatotropism and Diabetes Mellitus

“…The major form in blood is the nonoctanoylated or “inactive” form known as desacyl ghrelin. Nevertheless, increasing numbers of studies report also biological effects of desacyl ghrelin and studies in humans have shown that both forms are suppressed in acromegaly, justifying the use of a total ghrelin ELISA 11, 28, 29. The study employed, after approriate validation, a Rat/Mouse Ghrelin ELISA for measuring feline ghrelin.…”

“…The effect may be independent or could be confounded by changes in insulin secretion and sensitivity, as well as glycemic control, induced by HS and its treatment. Indeed, in humans, low ghrelin concentrations have been associated with insulin resistance and development of type 2 DM 14, 18, 28, 34. In addition, hyperinsulinemia, acute hyperglycemia and poor long‐term glycemic control in cats with DM might impair ghrelin secretion in humans 35, 36.…”