Effect of a 4‐methyl‐4‐aza steroid on androgen metabolism by rat ventral prostate epithelial and stromal cell cultures: Selective inhibition of 5α‐reductase activity
- 1 January 1988
- journal article
- research article
- Published by Wiley in The Prostate
- Vol. 13 (4), 289-297
- https://doi.org/10.1002/pros.2990130404
Abstract
The effect of a potent steroid metabolic inhibitor, 17β‐N,N‐diethylcarbamoyl‐4‐methyl‐4‐ aza‐5α‐androstan‐3‐one (DMAA), on androgen metabolism was investigated in primary monolayer cultures of rat ventral prostate epithelial and stromal cells. Using testosterone (T) as substrate, 5α‐reductase (5α‐R) activity in both cell types was inhibited by greater than 98% at an inhibitor concentration of 1000 nM. The concentrations required to produce a 50% inhibition (IC50) were 7.4 and 9.0 nM for epithelial and stromal cells, respectively. To examine the specificity of this compound, its effect on other steroid‐metabolic enzymes was examined. DMAA at a concentration of 1,000 nM had no effect on 3α‐hydroxysteroid oxidase (3α‐HSORox), 3‐ketosteroid reductase (3α‐HSORred), and 6/7‐hydroxylase (6/7‐HSH) activities in both cell types; 17β‐hydroxysteroid oxidase (17β‐HSORox) activity, located primarily in epithelial cells, also was not influenced by DMAA. In contrast, epithelial 3β‐hydroxysteroid oxidase (3β‐HSORox) and 3‐ketosteroid reductase (3β‐ HSORred) activities were inhibited by 65% (P < .001) and 58% (P > .05), respectively, albeit the latter result was not statistically significant. Stromal 3β‐HSORox and 3β‐ HSORred activities were negligible; hence the effect of the inhibitor on these enzymes could not be assessed. In conclusion, DMAA is a relatively selective and potent inhibitor of 5α‐R activity in primary cultures of rat ventral prostate epithelial and stromal cells and should be a useful compound for antagonizing androgen‐mediated actions in the prostate and other androgen target tissues.Keywords
This publication has 20 references indexed in Scilit:
- The effect of 4MA, a potent inhibitor of 5 alpha‐reductase, on the growth of androgen‐responsive human genitourinary tumors grown in athymic nude miceThe Prostate, 1987
- Androgen metabolism and actions in rat ventral prostate epithelial and stromal cell culturesBiochemistry and Cell Biology, 1986
- Biochemical and biological studies with 4-aza-steroidal 5α-reductase inhibitorsJournal of Steroid Biochemistry, 1983
- The role of androgen metabolism in the control of androgen action in the rat prostateMolecular and Cellular Endocrinology, 1982
- Effect of a new 5α-reductase inhibitor on size, histologic characteristics, and androgen concentrations of the canine prostateThe Prostate, 1982
- Stromal-Epithelial Interactions in Sex DifferentiationBiology of Reproduction, 1980
- ROLE OF THE MESENCHYME IN THE INDUCTION OF THE RAT PROSTATE GLAND BY ANDROGENS IN ORGAN CULTUREJournal of Endocrinology, 1979
- The identification and characterization of a new c1903 steroid metabolite in the eat ventral prostate: 5α-androstane-3β, 6α, 17β-triolSteroids, 1979
- In vivo metabolism of 3H-dihydrotestosterone and 3H-androstanediol in adult male ratsJournal of Steroid Biochemistry, 1975
- A comparative study of the ultrastructure and lack of growth capacity of adult human prostate epithelium mechanically separated from its stromaThe Journal of Pathology, 1970