Growth hormone secretagogue receptor 1 (GHSR1 (also commonly abbreviated as GHS-R1a for the active isoform))

The **Growth hormone secretagogue receptor 1** (**GHSR1**, often called the *ghrelin receptor*) is a class A rhodopsin-like **G protein-coupled receptor** that mediates the actions of ghrelin—a gut-derived peptide involved in stimulating appetite (“hunger hormone”), regulating energy balance/fat accumulation, modulating reward/mood circuits in the brain, promoting growth hormone release from the pituitary gland, and influencing glucose metabolism. The canonical active form is known as **GHSR1a**. This receptor exhibits complex signaling properties by coupling with several types of intracellular proteins (notably various subtypes of α subunits like Gαq/11—which increases intracellular calcium—and others), allowing it to regulate diverse physiological processes. It also displays high constitutive activity even without ligand binding. Importantly, it can form heterodimers with other GPCRs—including dopamine receptors—which further modulates its function. Because dysregulation of this pathway contributes to obesity and related metabolic diseases—and possibly neuropsychiatric conditions—the ghrelin/GHSR system has been extensively studied as a therapeutic target. However, drug development has been challenging due to pleiotropic effects across multiple organ systems and difficulties achieving selective modulation without adverse outcomes.

Other names

Ghrelin receptorGrowth hormone secretagogue receptorGHSRGHS-RGH-releasing peptide receptor

Agonists stimulate the receptor to increase growth hormone release, appetite, and energy storage via multiple intracellular pathways including activation of phospholipase C through Gαq/11 proteins leading to increased intracellular calcium; also activates other pathways via different G-protein couplings such as Gαi/o/z and Gα12/13; can recruit β-arrestin for alternative signaling or desensitization. Antagonists block these effects by inhibiting ghrelin binding or downstream signaling.