Inhibition of 5a‐Reductase Activity and Alteration of Nuclear Testosterone: Dihydrotestosterone Ratio in Human Genital Skin Fibroblasts

GARY D. BERKOVITZ; TERRY R. BROWN; AND CLAUDE J. MIGEON

doi:10.1002/j.1939-4640.1984.tb02389.x

Inhibition of 5a‐Reductase Activity and Alteration of Nuclear Testosterone: Dihydrotestosterone Ratio in Human Genital Skin Fibroblasts

GARY D. BERKOVITZ, TERRY R. BROWN, AND CLAUDE J. MIGEON

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

17 beta-N, N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA) inhibits 5 alpha-reductase activity in cultured human genital skin fibroblasts. Enzyme kinetic studies analyzed by Eadie-Hofstee plots demonstrated that 4-MA is a competitive inhibitor, with an apparent Ki of 15 nM. 4-MA had a very low binding affinity for the androgen receptor. When fibroblasts were incubated in the presence of testosterone (T) and 4-MA, nuclear uptake of 5 alpha-dihydrotestosterone (DHT) decreased in parallel with the inhibition of 5 alpha-reductase activity. While the overall sum for the nuclear uptake of T and DHT diminished, the nuclear uptake of T increased. Biological androgen inactivity cannot be precluded on the basis of nuclear T plus DHT uptake.

Original language	English (US)
Pages (from-to)	171-175
Number of pages	5
Journal	Journal of Andrology
Volume	5
Issue number	3
DOIs	https://doi.org/10.1002/j.1939-4640.1984.tb02389.x
State	Published - Jan 1 1984
Externally published	Yes

Keywords

5?‐reductase
androgen receptor
enzyme inhibitor
fibroblast
nuclear uptake

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Reproductive Medicine
Endocrinology
Urology

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title = "Inhibition of 5a‐Reductase Activity and Alteration of Nuclear Testosterone: Dihydrotestosterone Ratio in Human Genital Skin Fibroblasts",

abstract = "17 beta-N, N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA) inhibits 5 alpha-reductase activity in cultured human genital skin fibroblasts. Enzyme kinetic studies analyzed by Eadie-Hofstee plots demonstrated that 4-MA is a competitive inhibitor, with an apparent Ki of 15 nM. 4-MA had a very low binding affinity for the androgen receptor. When fibroblasts were incubated in the presence of testosterone (T) and 4-MA, nuclear uptake of 5 alpha-dihydrotestosterone (DHT) decreased in parallel with the inhibition of 5 alpha-reductase activity. While the overall sum for the nuclear uptake of T and DHT diminished, the nuclear uptake of T increased. Biological androgen inactivity cannot be precluded on the basis of nuclear T plus DHT uptake.",

keywords = "5?‐reductase, androgen receptor, enzyme inhibitor, fibroblast, nuclear uptake",

author = "BERKOVITZ, {GARY D.} and BROWN, {TERRY R.} and MIGEON, {AND CLAUDE J.}",

year = "1984",

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doi = "10.1002/j.1939-4640.1984.tb02389.x",

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TY - JOUR

T1 - Inhibition of 5a‐Reductase Activity and Alteration of Nuclear Testosterone

T2 - Dihydrotestosterone Ratio in Human Genital Skin Fibroblasts

AU - BERKOVITZ, GARY D.

AU - BROWN, TERRY R.

AU - MIGEON, AND CLAUDE J.

PY - 1984/1/1

Y1 - 1984/1/1

N2 - 17 beta-N, N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA) inhibits 5 alpha-reductase activity in cultured human genital skin fibroblasts. Enzyme kinetic studies analyzed by Eadie-Hofstee plots demonstrated that 4-MA is a competitive inhibitor, with an apparent Ki of 15 nM. 4-MA had a very low binding affinity for the androgen receptor. When fibroblasts were incubated in the presence of testosterone (T) and 4-MA, nuclear uptake of 5 alpha-dihydrotestosterone (DHT) decreased in parallel with the inhibition of 5 alpha-reductase activity. While the overall sum for the nuclear uptake of T and DHT diminished, the nuclear uptake of T increased. Biological androgen inactivity cannot be precluded on the basis of nuclear T plus DHT uptake.

AB - 17 beta-N, N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA) inhibits 5 alpha-reductase activity in cultured human genital skin fibroblasts. Enzyme kinetic studies analyzed by Eadie-Hofstee plots demonstrated that 4-MA is a competitive inhibitor, with an apparent Ki of 15 nM. 4-MA had a very low binding affinity for the androgen receptor. When fibroblasts were incubated in the presence of testosterone (T) and 4-MA, nuclear uptake of 5 alpha-dihydrotestosterone (DHT) decreased in parallel with the inhibition of 5 alpha-reductase activity. While the overall sum for the nuclear uptake of T and DHT diminished, the nuclear uptake of T increased. Biological androgen inactivity cannot be precluded on the basis of nuclear T plus DHT uptake.

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