FOLLITROPIN (FSH) DEFICIENCY IN AN INFERTILE MALE DUE TO FSH-BETA GENE MUTATION - A SYNDROME OF NORMAL PUBERTY AND VIRILIZATION BUT UNDERDEVELOPED TESTICLES WITH AZOOSPERMIA, LOW FSH BUT HIGH LUTROPIN AND NORMAL SERUM TESTOSTERONE CONCENTRATIONS

We studied a man who sought medical attention at age 28 years because of infertility in both his first and second marriages. His sexual deve lopment appeared to have been normal, with normal puberty and viriliza tion, and normal libido and sexual potency. At examination, his testic les were small and soft; otherwise he had a normal physical appearance . Evaluations revealed azoospermia, undetectable in serum before and a fter 100 mu g of intravenously administered gonadotrophin releasing ho rmone, but moderately elevated lutropin concentration with a brisk ris e after gonadotrophin releasing hormone. The a subunit concentration w as normal before and after gonadotrophin releasing hormone; that of in hibin B was very low. Analysis of the follitropin beta gene, exon 3, r evealed a Cys(82) --> Arg mutation (TGT --> CGT). Judging from studies of the biosynthesis of the chorionic gonadotrophin beta subunit one m ay conclude that inability to form the first intramolecular disulphide bond in the follitropin beta subunit results in an abnormal tertiary structure during follitropin beta biosynthesis with extensive intracel lular degradation of the products, inability to associate with the a s ubunit and defective glycosylation, as well as inability to form a bio logically active hormone. This first male case of follitropin deficien cy thus defines a new syndrome of male infertility.