Inhibition of 5 alpha-reductase activity and alteration of nuclear testosterone. Dihydrotestosterone ratio in human genital skin fibroblasts.
Inhibition of 5 alpha-reductase activity and alteration of nuclear testosterone. Dihydrotestosterone ratio in human genital skin fibroblasts.
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抑制 5α-还原酶活性和改变核睾酮。
DOI：
10.1002/j.1939-4640.1984.tb02389.x
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发表时间：
1984
影响因子：
--
通讯作者：
Migeon,CJ
中科院分区：
文献类型：
--
作者：
Berkovitz,GD;Brown,TR;Migeon,CJ
17β-N，N-二乙基氨基甲酰基-4-甲基-4-氮杂-5 α-雄甾烷-3-酮（4-MA）抑制培养的人生殖器皮肤成纤维细胞中的5α-还原酶活性。通过Eadie-Hofstee图分析的酶动力学研究表明，4-MA是一种竞争性抑制剂，表观Ki <15 nM。4-MA对雄激素受体的结合亲和力非常低。当成纤维细胞在睾酮（T）和4-MA的存在下孵育时，5α-二氢睾酮（DHT）的核摄取减少与5？还原酶活性虽然T和DHT的核摄取的总和减少，但T的核摄取增加。不能根据核T + DHT摄取排除生物雄激素无活性。
17β‐N, N‐diethylcarbamoyl‐4‐methyl‐4‐aza‐5α‐an‐drostan‐3‐one (4‐MA) inhibits 5α‐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 Kiof 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 5α‐dihydrotestosterone (DHT) decreased in parallel with the inhibition of 5?‐reduc‐tase 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.