No germ-line mutations of the glycoprotein hormone common a-subunit have been reported, apparently because of the dramatic phenotypic effects they would have (possibly embryo lethality). One inactivating LHfi mutation has been described in a man with normal prenatal masculinization but arrested pubertal development. Additional cases are needed before final conclusions about the phenotypic effect of missing LH action can be drawn. A common polymorphism exists in the LHP subunit. It affects bioactivity of the hormone and has multiple mild phenotypic effects, including slow tempo of puberty in boys. It may be a contributing factor to the heterogeneous pace of pubertal development. It is also enriched in postterm boys with cryptorchidism. The three men so far described with FSHfi mutation were azoospermic, but additional patients are needed to confirm the phenotype, particularly because this phenotype conflicts with the findings in FSH-R inactivation.
Constitutively activating mutations of the LH-R gene give rise to FMPP. Inactivating LH-R mutation results in an array of male phenotypes ranging from micropenis and hypospadias to complete sex reversal (XY, pseudohermaphroditism), depending on the completeness of inactivation of the receptor. Inactivating FSHR mutations in men cause a decrease of testicular size and suppressed quality and quantity of spermatogen-esis but not azoospermia. Some affected men may be fertile. FSH inactivation is unlikely to affect pubertal maturation. No unequivocally activating mutations of the FSHR have yet been described in either sex. Studies on candidate syndromes (e.g., precocious puberty and macro-orchia) have yielded negative results.
The discrepancy between the phenotypes of men with inactivating FSH ¡¡-submit (azoospermia) and FSH-R (no azoospermia) mutations must be clarified with additional subjects. The male and female phenotypes of activating FSH-R mutation must be established. In addition, the phenotypic effects, if any, of the number of common polymorphisms detected in genes of the gonadotropin subunits and their receptors must be explored in more detail.
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