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In vivo assay for conversion of testosterone to dihydrotestosterone by rat prostatic steroid 5α‐reductase and comparison of two inhibitors
Author(s) -
Toomey Richard E.,
Goode Robin L.,
Petrow Vladimir,
Neubauer Blake L.
Publication year - 1991
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.2990190107
Subject(s) - dihydrotestosterone , in vivo , testosterone (patch) , endocrinology , steroid , medicine , prostate , in vitro , reductase , 5 alpha reductase inhibitor , androgen , chemistry , finasteride , enzyme , pharmacology , biology , hormone , biochemistry , cancer , microbiology and biotechnology
An in vivo assay for steroid 5α‐reductase in rat ventral prostate has been developed and used to compare the inhibitory activity of N,N‐diethyl‐4–methyl‐3–oxo‐4–aza‐5 a‐andro‐stane‐17 β‐carboxamide (4–MA) and 6–methylene‐4–pregnene‐3,20–dione (LY207320). Immature rats (70–80 g) received test compounds 30 min prior to s.c. injection of [ 3 H]‐T. The rats were sacrificed 30 min later and the ventral prostates were analyzed for [ 3 H]‐T metabolites. Intraprostatic [ 3 H]‐T and [ 3 H]‐DHT reached peak levels within 5 min after injection of [ 3 H]‐T and declined to about 25% of peak levels after 2 hr. 4–MA was a very potent inhibitor of [ 3 H]‐DHT formation with an estimated IC 50 of 0.2 mg/kg. LY207320, an inhibitor of 5α‐reductase in vitro, was weakly active in vivo and did not achieve greater than 45% inhibition at high doses (> 200 mg/kg, s.c.). Tissue uptake of [ 3 H]‐T was also inhibited by LY207320, which may contribute to its inhibitory activity on accessory sex organ growth in the rat.