MOLECULAR ANDROLOGY: ADVANCES IN THE NEW MILLENNIUM

Recent advances in molecular andrology include several topics: neuroendocrinology of embryonic sexual di€ erentiation; pathophysiology of spermatogenesis; Leydig cells, Sertoli cells; oligoasthenoteratozoospermi a (OAT), genetic male infertility; stem cells; reactive oxygen species (ROS); clusterin andropause and erectile dysfunction (ED) [1, 3± 9, 11± 13]. LH, stimulated by hypothalamic GnRH, activates the Leydig cell cyclic adenosine monophosphate (cAMP) signal transduction pathway. cAMP then stimulates protein kinase A, which phosphorylates proteins. Phosphorylated proteins further phosphorylate other proteins or induce new protein synthesis, such as the steroidogenic acute regulatory (StAR) protein. The function of the StAR protein is to facilitate the transfer of free cholesterol from cytoplasm into the inner membrane of mitochondria where the cytochrome P450 sidechain cleavage enzyme converts cholesterol to pregnenolone. The translocation of cholesterol into mitochondria by StAR protein is a rate-limiting step in steroidogenesis. MuÈ llerian inhibiting substance (MIS) , or anti-MuÈ llerian hormone (AMH), is a 140-kD glycoprotein belonging to (TGF)-b family of growth/di€ erentiation factors. One such function is for MIS to directly inhibit adult Leydig cell steroidogenesis. During male sexual di€ erentiation, MIS causes regression of the MuÈ llerian ducts, the anlagen of the female internal reproductive tracts. The gonadal hormone has additional paracrine roles in postnatal testis. Testicular torsion, a pathologic condition in man, renders the testis ischemic, and surgical intervention is usually required to reestablish blood ̄ ow. Permanent loss of spermatogenesis is observed after torsion repair despite the return of blood ̄ ow and the maintenance of Leydig and Sertoli function. This loss of spermatogenesis is due to germ cell-speci® c apoptosis. This apoptosis is directly linked to the recruitment of