Evolution of the Growth Hormone Receptor Family

Abstract

The growth hormone receptor (GHR) family includes receptors for growth hormone and prolactin receptor (PRLR). GHRs and PRLRs are membrane receptors that possess several evolutionarily conserved features: a hormone‐binding extracellular domain, a single‐chain transmembrane domain and an intracellular domain important for activating intracellular signal systems that mediate cell‐specific responses. PRLRs diverged early from a common GHR/PRLR in jawless fish (e.g. Agnathans), followed by subsequent divergence of GHRs in the Actinopterygian lineage that gave rise to teleosts and in the Sarcopterygian lineage that gave rise to tetrapods. Structural heterogeneity of GHRs in teleosts results from the existence of multiple genes that arose through a series of independent gene duplication events during the course of their evolution and from alternative transcripts of a single gene. Differential receptor–ligand interactions, differential receptor–cell signalling system interactions and the differential expression of alternate GHR forms underlie the vast array of functions elicited by GH. Key Concepts Growth hormone regulates many processes, including growth, metabolism, osmoregulation, reproduction and behaviour. Growth hormone receptors are single‐pass membrane‐bound receptors that mediate the actions of growth hormone. The growth hormone receptor family arose through a series of gene duplication events during the course of vertebrate evolution. The multiple actions of growth hormone arise from binding to variant forms of growth hormone receptor and from activation of alternate cell signalling pathways.