The role of the follicle-stimulating hormone receptor in supporting male reproduction: A narrative review

The follicle-stimulating hormone receptor (FSHR) in the testis is expressed exclusively in Sertoli cells. Follicle-stimulating hormone (FSH) is mediated by FSHR via the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA), mammalian target of rapamycin complex 1 (mTORC1), and AMP-activated protein kinase (AMPK) signaling pathways to induce the proliferation and maturation of immature Sertoli cells. In addition, FSH and androgens regulate spermatogenesis in an overlapping and synergistic manner. Based on these physiological mechanisms, mutations in the FSHβ subunit often lead to azoospermia; activating mutations in the gene encoding FSHR can render spermatogenesis independent of FSH; inactivating mutations can impair male spermatogenic function; and single nucleotide polymorphisms vary by genetic background and ethnicity, with no consistent conclusions regarding their relationship with male infertility. This review suggests that FSHR modulators hold profound significance for the future diagnosis and treatment of infertility and may provide new avenues for male contraception.