Seiffert K, Seltmann H, Fritsch M, Zouboulis C C
Division of Dermatology and Cutaneous Sciences, Michigan State University, East Lansing MI, USA.
Horm Metab Res. 2007 Feb;39(2):141-8. doi: 10.1055/s-2007-961814.
Inhibition of 5alpha-reductase type 1 has been considered to be a promising target for treatment of androgen-dependent skin disorders, however, currently published clinical results on acne treatment are rather disappointing. In this study, the influence of selective inhibitors of 5alpha-reductase on testosterone metabolism within SZ95 sebocytes and HaCaT keratinocytes IN VITRO was investigated. In both cell types, the isotype 1 inhibitor MK386 completely inhibited the conversion of testosterone to 5alpha-dihydrotestosterone in concentrations higher than 10 (-9) M. Inhibitors of the isotype 2 such as finasteride, dihydrofinasteride, and turosteride, were >100-fold less active, while, as expected, androgen receptor inhibitors did not affect the 5alpha-reductase activity. MK386, but not finasteride, reduced testosterone-stimulated proliferation and slightly reduced the testosterone-induced increase in the amount of SZ95 sebocyte proteins. The androgen receptor inhibitor cyproterone acetate exhibited no effect on testosterone-induced proliferation, but inhibited the 5alpha-dihydrotestosterone-induced sebocyte proliferation. Our experimental findings and the existing clinical results indicate that the inhibition of 5alpha-reductase activity alone may be insufficient to reduce overall sebocyte activity and improve acne lesions.
1型5α-还原酶的抑制作用被认为是治疗雄激素依赖性皮肤疾病的一个有前景的靶点，然而，目前已发表的关于痤疮治疗的临床结果相当令人失望。在本研究中，研究了5α-还原酶选择性抑制剂对体外培养的SZ95皮脂腺细胞和HaCaT角质形成细胞内睾酮代谢的影响。在两种细胞类型中，1型抑制剂MK386在浓度高于10（-9）M时完全抑制睾酮向5α-二氢睾酮的转化。2型抑制剂如非那雄胺、二氢非那雄胺和图司他胺的活性低100倍以上，而正如预期的那样，雄激素受体抑制剂不影响5α-还原酶活性。MK386而非非那雄胺可降低睾酮刺激的增殖，并略微降低睾酮诱导的SZ95皮脂腺细胞蛋白量的增加。雄激素受体抑制剂醋酸环丙孕酮对睾酮诱导的增殖无影响，但可抑制5α-二氢睾酮诱导的皮脂腺细胞增殖。我们的实验结果和现有的临床结果表明，仅抑制5α-还原酶活性可能不足以降低整体皮脂腺细胞活性并改善痤疮皮损。
