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Int J Cosmet Sci. 2000 Dec;22(6):397-407.
The steroid 5alpha-reductase isoenzymes (5alphaR) transform testosterone into 17beta-hydroxy-5alpha-androstan-3-one (5-dihydrotestosterone, DHT), which exerts a much stronger biological activity than does testosterone. Briefly, the two 5alphaR isoenzymes are differentially expressed in the two major target organs of steroid action, the prostate (isoenzyme 2, 5alphaR2) and the skin (isoenzyme 1, 5alphaR1). We analysed the potential of a human epidermal tissue reconstituted by cell culture (RHE, provided by SkinEthic Laboratories, Nice, France) as a model for assessing 5alphaR activity. The epidermal model was found to express the type-1 (skin) isoform of 5alphaR and thus could be used as an enzyme source for the screening of 5alphaR modulators for dermatological/cosmetic purposes. A reproducible and convenient assay method was developed, allowing both the evaluation of testosterone transformation into DHT (5alphaR activity) and an outlook on the general metabolism process of testosterone. This could be important for the detection of any compound that could act mainly on another target enzyme than 5alphaR. The assay gave evidence of the inhibitory activity of finasteride against type-1 5alphaR, which is now established both in vitro and in clinical studies. In addition to enzyme inhibitors, this in situ cellular assay can detect transcriptional modulators of 5alphaR gene expression, or any compound that could modulate enzyme processing or post-translational activation. RT-PCR analysis of RNA samples from RHE failed to show any notable effect of finasteride, testosterone, or DHT treatment on the expression of 5alphaR1 at the transcriptional level.
5α-还原酶同工酶（5αR）将睾酮转化为 17β-羟基-5α-雄烷-3-酮（5-二氢睾酮，DHT），其生物活性比睾酮强得多。简而言之，这两种 5αR 同工酶在甾体作用的两个主要靶器官中差异表达，即前列腺（同工酶 2，5αR2）和皮肤（同工酶 1，5αR1）。我们分析了由细胞培养重建的人表皮组织（由 Nice，法国的 SkinEthic 实验室提供的 RHE）作为评估 5αR 活性的模型的潜力。发现表皮模型表达 1 型（皮肤）同工酶的 5αR，因此可以用作筛选用于皮肤学/化妆品目的的 5αR 调节剂的酶源。开发了一种可重复且方便的测定方法，允许评估睾酮转化为 DHT（5αR 活性），并展望睾酮的一般代谢过程。这对于检测任何主要作用于 5αR 以外的靶酶的化合物可能很重要。该测定法证明了非那雄胺对 1 型 5αR 的抑制活性，这在体外和临床研究中均已得到证实。除了酶抑制剂之外，这种原位细胞测定法还可以检测 5αR 基因表达的转录调节剂，或任何可以调节酶处理或翻译后激活的化合物。RHE 的 RNA 样品的 RT-PCR 分析未能显示非那雄胺、睾酮或 DHT 处理对 5αR1 转录水平表达的任何显著影响。
