GHSR1b

GHSR1b, also known as ghrelin receptor 1b, is an alternatively spliced isoform of the growth hormone secretagogue receptor (GHSR) gene. It is related to the signaling-competent GHSR1a receptor but encodes a truncated form that generally lacks the intracellular domains necessary for classical G protein–coupled signaling. As a result, GHSR1b is typically considered unable to initiate the canonical cellular responses to ghrelin on its own.

Structure and expression: GHSR1b arises from the same gene as GHSR1a and shares portions of the receptor sequence, but its truncated intracellular region impairs signaling. It is expressed in various tissues, including brain and peripheral organs, with expression patterns that can differ by species and physiological state.

Function and mechanisms: The leading view is that GHSR1b modulates ghrelin signaling rather than acting as an independent receptor. It can form heterodimers with GHSR1a, influencing receptor trafficking to the cell surface, ligand binding, and downstream signaling. In many experimental systems, co-expression of GHSR1b reduces GHSR1a-mediated responses such as calcium mobilization and cAMP production, suggesting a potential dominant-negative or regulatory role. The precise physiological significance of these interactions remains an area of active research.

Clinical and research context: Investigations into GHSR1b contribute to understanding appetite regulation, energy balance, and growth hormone axis control. Altered expression or interactions with GHSR1a have been studied in animal models of metabolic disorders, though direct causal relationships to human disease are not yet established.

See also: GHSR, GHSR1a, ghrelin, growth hormone secretagogue receptor.