Luteinizing hormone/choriogonadotropin receptor

The luteinizing hormone/choriogonadotropin receptor (LHCGR), also lutropin/choriogonadotropin receptor (LCGR) or luteinizing hormone receptor (LHR) is a transmembrane receptor found predominantly in the ovary and testis, but also many extragonadal organs such as the uterus and breasts. The receptor interacts with both luteinizing hormone (LH) and chorionic gonadotropins (such as hCG in humans) and represents a G protein-coupled receptor (GPCR). Its activation is necessary for the hormonal functioning during reproduction. The gene for the LHCGR is found on chromosome 2 p21 in humans, close to the FSH receptor gene. It consists of 70 kbp (versus 54 kpb for the FSHR). The gene is similar to the gene for the FSH receptor and the TSH receptor. The LHCGR consists of 674 amino acids and has a molecular mass of about 85–95 kDA based on the extent of glycosylation. Like other GPCRs, the LHCG receptor possess seven membrane-spanning domains or transmembrane helices. The extracellular domain of the receptor is heavily glycosylated. These transmembrane domains contain two highly conserved cysteine residues, which build disulfide bonds to stabilize the receptor structure. The transmembrane part is highly homologous with other members of the rhodopsin family of GPCRs. The C-terminal domain is intracellular and brief, rich in serine and threonine residues for possible phosphorylation. Upon binding of LH to the external part of the membrane spanning receptor, a transduction of the signal takes place. This process results in the activation of a heterotrimeric G protein. Binding of LH to the receptor shifts its conformation. The activated receptor promotes the binding of GTP to the G protein and its subsequent activation. After binding GTP, the G protein heterotrimer detaches from the receptor and disassembles. The alpha-subunit Gs binds adenylate cyclase and activates the cAMP system. It is believed that a receptor molecule exists in a conformational equilibrium between active and inactive states.