Commentary Extragonadal FSH Receptor: Is It Real?1

Follicle-stimulating hormone (FSH) is a pituitary gonado-troph-derived heterodimeric glycoprotein that binds G protein-coupled FSH receptors (FSHRs) on ovarian granulosa cells [1– 3]. This FSH/FSHR signaling pathway is essential for female fertility because null mice lacking either the FSH ligand [4] or FSHR [5, 6] are sterile as a result of preantral stage block in ovarian folliculogenesis. These FSH ligand/receptor null mice phenocopy women harboring inactivating mutations (homo-zygous recessive) in corresponding alleles encoding the hormone-specific FSH beta subunit and FSHR [7, 8]. A number of in vitro and in vivo studies have documented the cascade of signaling events elicited by FSH binding to FSHRs on granulosa cells [2, 3, 9]. Although the predominant signaling pathway activated by FSH is cAMP-mediated phosphorylation of PKA and CREB, activation of othe