THE LUTEINIZING-HORMONE RECEPTOR

The luteinizing hormone receptor (LHR) is a member of the subfamily of glycoprotein hormone receptors within the superfamily of G protein-co upled receptor (GPCR)/seven-transmembrane domain receptors. Over the p ast eight years, major advances have been made in determining the stru cture and function of the LHR and its gene. The hormone-binding domain has been localized to exons 1-7 in the extracellular (EC) domain/regi on of the receptor, which contains several leucine-rich repeats. High- affinity binding of LH and human chorionic gonadotropin (hCG) causes s econdary hormone or receptor contacts to be established with regions o f the EC loop/transmembrane module that initiate signal transduction. Models of hormone-receptor interaction have been derived from the crys tal structures of hCG and of the ribonuclease inhibitor, which also co ntains leucine-rich repeats. Such models provide a framework for the i nterpretation of mutational studies and for further experiments. The e xtracellular domain of the receptor has been overexpressed in vitro, w hich will facilitate crystallographic resolution of the structure of t he receptor-binding site. The transmembrane domain/loop/cytoplasmic mo dule transduces the signal for coupling to G proteins. Several constit utive, activating mutations that cause human disease have been found i n helix VI and adjacent structures. These mutations have provided valu able information about mechanisms of signal transfer and G protein cou pling. The structure of the LHR gene has been elucidated, and the regu lation of its transcription is beginning to be understood. Valuable in sights into receptor evolution have been derived from analysis of sequ ence homologies, the gene structure of glycoprotein hormone receptors and other members of the GPCR family, and the glycoprotein hormone rec eptor-like precursors identified in several invertebrate species.