In vitro studies on the inhibition of testosterone synthesis in the human testis by atamestane.
In view of the well established clinical results of the deprivation of androgens through orchiectomy in prostatic cancer and the structural similarities of 4-androsten-3,17-dione and atamestane (1-methyl-ADD), we studied the influence of 1-methyl-ADD on the conversion of 4-androsten-3,17-dione to testosterone by the 17 beta-hydroxysteroid reductase enzyme in human testicular tissue. Our studies, presented in this manuscript, demonstrate that 1-methyl-ADD is a competitive inhibitor of 4-androsten-3,17-dione in its reduction to testosterone by the 17 beta-hydroxysteroid reductase enzyme in the human testis.
Department of Surgery, University of South Florida, College of Medicine.
M E
ME
Lombardo
S I
SI
Hakky
P B
PB
Hudson
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000368:Aged; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000601:surgery; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
D013739:Testosterone; D000735:Androstenedione; C048751:atamestane; D015067:17-Hydroxysteroid Dehydrogenases; C032690:3-alpha-(17-beta)-hydroxysteroid dehydrogenase (NAD(+))