FSHR

FSHR, or follicle-stimulating hormone receptor, is a G protein-coupled receptor that binds follicle-stimulating hormone (FSH). It is encoded by the FSHR gene, located on chromosome 2p21, and is primarily expressed in gonadal tissues—granulosa cells of the ovary and Sertoli cells of the testis. Through FSHR signaling, FSH promotes follicular growth, estrogen production, and spermatogenesis, supporting both female and male reproductive development.

Structurally, FSHR is a seven-transmembrane GPCR. The extracellular N-terminal domain contains leucine-rich repeats responsible for high-affinity hormone binding, while the seven transmembrane helices transmit the signal across the cell membrane. Upon FSH binding, the receptor mainly activates the Gs protein, stimulating adenylate cyclase, increasing cAMP, and triggering protein kinase A–dependent transcriptional programs. Other signaling routes, including beta-arrestin–mediated pathways and MAPK cascades, have also been described in certain contexts.

Genetic variation in FSHR influences receptor function and reproductive biology. Common polymorphisms, notably Asn680Ser (rs6166) and Thr307Ala (rs6165), are associated with differences in ovarian response to FSH during assisted reproduction technologies and in menstrual cycling. Loss-of-function mutations in FSHR can cause gonadal resistance to FSH, leading to infertility with hypergonadotropic hypogonadism, whereas activating mutations may cause conditions such as familial spontaneous ovarian hyperstimulation syndrome, including heightened ovarian sensitivity to FSH.

Clinically, FSHR is a key mediator of fertility treatments, as recombinant FSH therapies rely on functional FSHR to induce follicular recruitment and maturation. Ongoing research explores additional tissue distribution, receptor regulation, and the full spectrum of signaling pathways engaged by FSHR.