Pseudohypoparathyroidism: Mutation affecting adenylate cyclase

Pseudohypoparathyroidism, type I (PHP-I), is a rare hereditary disorder characterized by resistance to parathyroid (PTH) and to other hormones that work by stimulating adenylate cyclase. Recent elucidation of the membrane proteins that comprise hormone-sensitive adenylate cyclase made it possible to define the molecular defect that causes resistance to hormones in most patients with PHP-I. This review will summarize the biochemical and clinical evidence that PHP-I results from deficient activity of the guanine nucleotide-binding protein that couples hormone receptors and the catalytic unit of adenylate cyclase.