Inactivating FSH receptor mutations and gonadal dysfunction

A variety of mutations and polymorphisms of genes regulating female and mal e reproductive functions have been discovered during the last few years. Th ese include several inactivating and activating mutations in LH receptor ge nes. The first mutation of FSH receptor (FSHR) gene was discovered in six F innish families. This inactivating Ala189Val transition in the extracellula r receptor domain causes primary amenorrhea, arrest of follicular developme nt and infertility in homozygous women. In contrast to females, this mutati on did not cause absolute infertility in males but only surpressed spermato genesis. Another inactivating mutation of the FSHR gene has been found at p osition 191 (Asn191Ile) in a healthy fertile woman. The studies on inactiva ting FSHR mutations demonstrate that normal ovarian function is critically dependant on FSH while, in contrast to earlier views, male fertility is les s strictly dependent on normal FSH action. (C) 1998 Elsevier Science Irelan d Ltd. All rights reserved.