5 Alpha-reductase inhibitory and antiandrogenic activities of novel steroids in hamster seminal vesicles.
The pharmacological activity of several 16-bromosubstituted trienediones 4 and 5, 16-methyl substituted dienediones 6 and 7 and the 16-methyl substituted trienedione 8 was determined on gonadectomized hamster seminal vesicles by measuring the in vitro conversion of testosterone (T) to dihydrotestosterone (DHT) as 5alpha-reductase inhibitors and also the ability of these steroids to bind to the androgen receptor. Steroids 6 and 7 when injected together with T decreased the weight of the seminal vesicles thus showing an antiandrogenic effect. Compounds 5 and 6 reduced substantially the conversion of T to DHT and therefore can be considered good inhibitors for the enzyme 5alpha-reductase; however both steroids failed to form a complex with the androgen receptor. On the other hand compound 7 which showed a very small inhibitory activity for the enzyme 5alpha-reductase, exhibited a very high affinity for the androgen receptor and thus can be considered an effective antiandrogen. This compound also reduced substantially the weight of the seminal vesicles. Steroids 4 and 8 did not reduce the weight of the seminal vesicles and exhibited a low affinity for the androgen receptor; 8 showed a weak 5alpha-reductase inhibitory activity, whereas 4 exhibited a weak androgenic effect.
Cabeza
Marisa
M
Department of Biological Systems, Metropolitan University-Xochimilco, Mexico DF.
Bratoeff
Eugene
E
Flores
Eugenio
E
Ramírez
Elena
E
Calleros
Jorge
J
Montes
Diana
D
Quiroz
Alexandra
A
Heuze
Ivonne
I
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D012669:Seminal Vesicles / Q000187:drug effects* / Q000201:enzymology*; D013256:Steroids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D004791:Enzyme Inhibitors; D013256:Steroids; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase