Principles of Endocrinology and Hormone Action

Abstract

G protein-coupled receptors (GPCRs) include one of the largest gene families in the mammalian genome. The diversity of receptor binding sites and coupling mechanisms provides the signaling specificity necessary to maintain homeostasis. Various G protein-coupled receptors are critical for the functioning of every endocrine system in health and disease, and these proteins are the predominant targets of therapeutic drugs. GPCRs are grouped by primary sequence into different families that all have a canonical seven alpha helical transmembrane domain structure. In recent years, solving the crystal structure for an increasing number of these receptors has helped to resolve the molecular mechanisms of ligand interaction and activation. Despite their name, they couple to cellular signaling via both heterotrimeric G proteins and G protein-independent mecha- nisms. Receptor and signaling regulatory mechanisms contribute to controlling the level of the cellular responses elicited. A variety of endocrine and systemic diseases are caused by specific receptor mutations