Mutations in G proteins and G protein-coupled receptors in endocrine disease.

G Proteins couple receptors for diverse extracellular signals to effecters such as enzymes and ion channels. The majority of polypeptide hormones, all monoamine neurotransmitters, PGs, and even extracellular Ca’+ signal their target cells through G protein-coupled receptors (GPCR). In the past few years, mutations in G proteins and GPCR have been identified as the causes of several endocrine diseases. Understanding the molecular basis of these diseases provides valuable insights into G protein and GPCR structure and function, and may be important for diagnosis and treatment. In this paper, I briefly describe G protein-coupled signal transduction, provide a general framework for understanding how G protein and GPCR mutations cause endocrine disease, review specific endocrine disorders caused by G protein and GPCR mutations, and speculate on implications of this work for the etiology, diagnosis, and treatment of endocrine disorders.