Ovarian dysfunction by activating mutation of GS alpha: McCune-Albright syndrome as a model

The McCune-Albright syndrome is characterized by cafe-au-lait spots, precocious puberty, and fibrous dysplasia. It is due to mutations in the gene encoding the GS protein alpha subunit coupling 7-transmembrane-domain receptors to adenylate cyclase, leading to constitutive adenylate cyclase activation and cAMP overproduction. Endocrinologists and gynecologists are confronted with new issues when these children reach adulthood. Gonadal function and fertility are often abnormal in women in whom puberty was precocious, owing to the persistence of a variable degree of ovarian autonomy that hinders adequate follicular development and ovulation.