TY - JOUR T1 - The Follitropin Receptor: Matching Structure and Function JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.116.104398 SP - mol.116.104398 AU - Alfredo Ulloa-Aguirre AU - Teresa Zarinan Y1 - 2016/01/01 UR - http://molpharm.aspetjournals.org/content/early/2016/07/05/mol.116.104398.abstract N2 - Follitropin, or follicle-stimulating hormone (FSH) receptor (FSHR), is a G protein-coupled receptor belonging to the glycoprotein hormone receptor family that plays an essential role in reproduction. Although its primary location is the gonad, the FSHR has also been reported in extragonadal tissues including bone, placenta, endometrium, liver, and blood vessels from a number of malignant tumors. The recently resolved crystal structure of FSH bound to the entire FSHR ectodomain has been instrumental in more clearly defining the role of this domain in ligand binding and receptor activation. Biochemical, biophysical and structural data also indicate that the FSHR exists as a higher order structure, and that it may heterodimerize with its closely related receptor, the luteinizing hormone receptor; this association may have physiological implications during ovarian follicle maturation given that both receptors coexist in the same cell. FSHR heterodimerization is unique to the ovary since in the testes, gonadotropin receptors are expressed in separate compartments. FSHR self-association appears to be required for receptor coupling to multiple effectors and adaptors, for the activation of multiple signaling pathways and the transduction of asymmetric signaling, and for negative and positive receptor cooperativity. It also provides a mechanism through which the glycosylation variants of FSH may exert distinct and differential effects at the target cell level. Given its importance in regulating activation of distinct signaling pathways, functional selectivity at the FSHR is briefly discussed, as well as the potential implications of this particular functional feature on the design of new pharmacological therapies in reproduction. ER -