title: Of marsupials and men: "Backdoor" dihydrotestosterone synthesis in male sexual differentiation.
abstract: Following development of the fetal bipotential gonad into a testis, male genital differentiation requires testicular androgens. Fetal Leydig cells produce testosterone that is converted to dihydrotestosterone in genital skin, resulting in labio-scrotal fusion. An alternative 'backdoor' pathway of dihydrotestosterone synthesis that bypasses testosterone has been described in marsupials, but its relevance to human biology has been uncertain. The classic and backdoor pathways share many enzymes, but a 3α-reductase, AKR1C2, is unique to the backdoor pathway. Human AKR1C2 mutations cause disordered sexual differentiation, lending weight to the idea that both pathways are required for normal human male genital development. These observations indicate that fetal dihydrotestosterone acts both as a hormone and as a paracrine factor, substantially revising the classic paradigm for fetal male sexual development.
authors: Department of Medicine, Division of Endocrinology, University of Fribourg, Chemin du Musee 5, 1700 Fribourg, Switzerland. anna.lauber@unifr.ch
authors: Anna
authors: A
authors: Biason-Lauber
authors: Walter L
authors: WL
authors: Miller
authors: Amit V
authors: AV
authors: Pandey
authors: Christa E
authors: CE
authors: Flück
mesh_terms: D000728:Androgens / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism*; D012734:Disorders of Sex Development; D005837:Genitalia, Male / Q000196:embryology*; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics*; D008297:Male; D012733:Sex Differentiation / Q000235:genetics*; D046468:Sexual Development / Q000235:genetics* / Q000502:physiology; D013737:Testis / Q000196:embryology; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
chemical_list: D000728:Androgens; D013196:Dihydrotestosterone; D006913:Hydroxysteroid Dehydrogenases; C435496:AKR1C2 protein, human; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)