Ghrelin

Endogenous Hormone

Ghrelin is a 28-amino-acid peptide hormone produced predominantly by specialized (X/A-like) cells of the stomach lining, with smaller amounts made in the small intestine, pancreas, and brain. It is the endogenous ligand for the growth hormone secretagogue receptor (GHSR-1a) and holds a unique place in physiology: it is the only well-characterized circulating hormone that reliably increases appetite. Ghrelin levels rise during fasting and immediately before expected meals, then fall after eating, which is why it is often called the 'hunger hormone.' Because it is a natural hormone the body makes itself, ghrelin is not sold or used as a drug — this page is an educational reference to the biology that synthetic secretagogues and appetite-modulating medicines are designed around. Ghrelin's activity depends on an unusual post-translational modification. To bind and activate GHSR-1a, the peptide must be acylated with a fatty acid (octanoic acid) on its third amino acid (serine-3). This step is carried out by the enzyme ghrelin O-acyltransferase (GOAT), and only this octanoylated form — known as acyl-ghrelin — stimulates the receptor. The non-acylated form (des-acyl ghrelin) circulates in larger amounts but does not activate GHSR-1a in the classical way, and its physiological role is still being worked out. This acylation requirement makes ghrelin biochemically distinct from the small-molecule and peptide secretagogues studied in the research space. Functionally, ghrelin has two headline effects. First, acting on GHSR-1a in the anterior pituitary, it stimulates the release of growth hormone (GH) — the property that gave the receptor its name and inspired an entire class of 'growth hormone secretagogues.' Second, acting on GHSR-1a in the hypothalamus (particularly on NPY/AgRP neurons of the arcuate nucleus), it drives hunger and food-seeking behavior and promotes fat storage. Ghrelin also influences gastric motility, insulin and glucose handling, reward pathways, and stress responses, which is why it sits at the center of gut–brain appetite signaling. You can read more about this system in our overview of the gut–brain axis and the explainer ghrelin, the hunger hormone. Because ghrelin defines the GHSR-1a mechanism, it is the reference point for many peptides covered on this site. Synthetic agonists mimic it for different goals: macimorelin is an FDA-approved oral diagnostic for growth hormone deficiency; anamorelin is an oral agonist approved in Japan for cancer cachexia; relamorelin is an injectable investigational prokinetic for gastroparesis; and research-grade secretagogues such as ipamorelin and ibutamoren target the same receptor for GH-related goals. Understanding ghrelin itself clarifies what all of these compounds are trying to reproduce — and where the biology stops and clinical evidence begins.