title: Steroidal 5α-reductase inhibitors using 4-androstenedione as substrate.
abstract: The aim of this study was to determine the capacity of some progesterone derivatives, to inhibit the conversion of labeled androstenedione ([(3)H] 4-dione) to [(3)H]dihydrotestosterone ([(3)H]DHT) in prostate nuclear membrane fractions, where the 5α-reductase activity is present. The enzyme 5α-reductase catalyzes the 5α-reduction of 4-dione whereas the 17β-hydroxysteroid dehydrogenase catalyzes the transformation of 4-dione to testosterone or 5α-dione to dihydrotestosterone (DHT). Moreover, we also investigated the role of unlabeled 5α-dione in these pathways. In order to determine the inhibitory effect of different concentrations of the progesterone derivatives in the conversion of [(3)H] 4-dione to [(3)H]DHT, homogenates of human prostate were incubated with [(3)H] 4-dione, NADPH and increasing concentrations of non-labeled 5α-dione. The incubating mixture was extracted and purified using thin layer chromatography. The fraction of the chromatogram corresponding to the standard of DHT was separated and the radioactivity determined. The results showed that the presence of [(3)H] 4-dione plus unlabelled 5α-dione produced similar levels of DHT as compared to [(3)H] 4-dione. On the other hand, the results indicated that 17α-hydroxypregn-4-ene-3,20-dione 5 and 4-bromo-17α-hydroxypregn-4-ene-3,20-dione 7b, were the most potent steroids to inhibit the conversion of [(3)H] 4-dione to [(3)H]DHT, showing IC(50) values of 2 and 1.6 nM, respectively.
authors.affiliation: Department of Biological Systems and Animal Production, Metropolitan University-Xochimilco, Mexico D. F., Mexico. marisa@correo.xoc.uam.mx
authors.forename: Marisa
authors.initials: M
authors.lastname: Cabeza
authors.forename: Karla Valeria
authors.initials: KV
authors.lastname: Trejo
authors.forename: Claudia
authors.initials: C
authors.lastname: González
authors.forename: Perla
authors.initials: P
authors.lastname: García
authors.forename: Juan
authors.initials: J
authors.lastname: Soriano
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Heuze
authors.forename: Eugene
authors.initials: E
authors.lastname: Bratoeff
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D000328:Adult; D000735:Androstenedione / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D015394:Molecular Structure; D009685:Nuclear Envelope / Q000201:enzymology; D011467:Prostate / Q000378:metabolism
chemical_list: D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D000735:Androstenedione