title: Androgenic and anti-androgenic effects of progesterone derivatives with different halogens as substituents at the C-6 position.
abstract: The pharmacological activities of four pregnane derivatives: 17alpha-hydroxy-16beta-methylpregna-4,6-diene-3,20-dio ne (7), 17alpha-acetoxy-16beta-methylpregna-4,6-diene-3,20-dio ne (8), 17alpha-acetoxy-6-bromo-16beta-methylpregna-4,6-diene- 3,20-dione (10), and 17alpha-acetoxy-6-chloro-16beta-methylpregna-4,6-diene -3,20-dione (11), were determined. The derivatives were evaluated on gonadectomized male hamster flank organs and seminal vesicles. The results indicate that topical applications of testosterone (T) on the flank organs increased the diameter of the pigmented spot. Similarly, the same phenomenon occurred on the glands treated with compound 11, whereas compound 10 decreased the size of the spot significantly. In this study, we determined the effects of several new steroids on the conversion of T to DHT in flank organs and seminal vesicles. The results show that compound 10 inhibited T conversion to DHT, but compound 11, at a dose of 200 microg, stimulated T conversion in both flank organs and seminal vesicles. However, when 2 mg of compound 11 was applied, it inhibited the conversion of T to DHT, suggesting that this compound also represses gonadotropin release. The difference between compounds 10 and 11 involves the electronegativity of the halogen at the C-6 position of the progesterone skeleton. These data clearly indicate that by decreasing the electronegativity of the halogen at C-6 (compound 10), 5alpha-reductase is inhibited in both tissues and at different pHs. On the other hand, when the electronegativity of the halogen atom was increased (11), there was a much lower inhibitory effect on the conversion of T to DHT.
authors.affiliation: Department of Biological Systems, Metropolitan University-Xochimilco and Faculty of Chemistry, National University of Mexico, Mexico, DF. marisa@cueyatl.uam.mx
authors.forename: M
authors.initials: M
authors.lastname: Cabeza
authors.forename: E
authors.initials: E
authors.lastname: Gutiérrez
authors.forename: R
authors.initials: R
authors.lastname: Miranda
authors.forename: I
authors.initials: I
authors.lastname: Heuze
authors.forename: E
authors.initials: E
authors.lastname: Bratoeff
authors.forename: G
authors.initials: G
authors.lastname: Flores
authors.forename: E
authors.initials: E
authors.lastname: Ramírez
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology*; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D006224:Cricetinae; D013196:Dihydrotestosterone / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D010858:Pigmentation / Q000187:drug effects; D011278:Pregnanes / Q000737:chemistry / Q000494:pharmacology*; D011374:Progesterone / Q000031:analogs & derivatives / Q000494:pharmacology; D012669:Seminal Vesicles / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D011278:Pregnanes; D013196:Dihydrotestosterone; D013739:Testosterone; D011374:Progesterone