Follicle-stimulating hormone ligand and receptor mutations, and gonadal dysfunction

In contrast to the general contention, infertility can be an inherited cond ition. Same of the genetic causes of male and female infertility have turne d out to be due to inactivating mutations in the gonadotropin and gonadotro pin receptor genes. The topic of the present text is to review current know ledge on mutations affecting the function of follicle-stimulating hormone ( FSH). This gonadotropin, by binding to its specific G protein-coupled cell membrane receptor (FSHR), is important for normal gonadal function. Mutatio ns affecting gonadotropin genes are extremely rare, but recent genetic stud ies have revealed that the pathogenesis of subfertility or infertility can be due to mutations in the FSH receptor (FSHR) gene. While mutations affect ing FSHR are sporadic, polymorphism of the FSHR gene seems to be a common p henomenon. To date, six inactivating and only one activating mutation have been detected in the FSHR gene. In contrast to LHR gene, the majority of th ese mutations affect the extracellular domain of the receptor. Together wit h animal models using the transgenic and knock-out approaches, systematic a nalysis of alterations in the FSHR gene increases our knowledge on the stru cture and function of the FSHR and demonstrates that the integrity of each FSHR segment is required for proper expression of the fully active protein and for normal gonadal function. Mutations in the FSHR gene have different consequences in the reproductive function depending on the sex of the patie nt: while normal ovarian function is critically dependent on FSH, male fert ility is possible with minimal or absent FSH action. (C) 2000 IMSS. Publish ed by Elsevier Science Inc.