GHRL

GHRL, commonly referred to as ghrelin, is a peptide hormone encoded by the GHRL gene. In humans, it is produced mainly by specialized cells in the stomach (gastric X/A-like cells) and released into the circulation in response to energy status. Ghrelin exists in two major circulating forms: acyl ghrelin, which carries an essential n-octanoyl group at serine-3 and is active at the growth hormone secretagogue receptor (GHSR1a); and desacyl ghrelin, which lacks this modification and has less clearly defined activity at GHSR1a but may act through other receptors or mechanisms.

Biosynthesis begins with the GHRL gene encoding preproghrelin, which is processed to proghrelin and then to the mature peptide ghrelin. The enzyme ghrelin O-acyltransferase (GOAT) adds the onyl group to produce acyl ghrelin. A related peptide, obestatin, is derived from the same gene precursor, though its physiological role remains debated.

Ghrelin exerts its primary effects through the growth hormone secretagogue receptor (GHSR1a), found in the pituitary and various brain regions. Binding to GHSR1a stimulates growth hormone release and activates neural circuits in the hypothalamus that promote appetite and energy intake, partly by interacting with neuropeptide Y/Agouti-related peptide neurons and influencing POMC/CART pathways. Beyond appetite, ghrelin influences gastric motility, gastrointestinal function, and glucose and lipid metabolism, contributing to energy homeostasis and feeding behavior.

Circulating ghrelin levels rise during fasting and fall after meals. They are typically reduced in obesity and can be altered in conditions such as cachexia and Prader-Willi syndrome. Research continues into ghrelin’s potential as a therapeutic target, including ghrelin agonists for weight gain and GOAT inhibitors for weight reduction.