Expression of type 1 5-alpha-reductase and metabolism of testosterone in reconstructed human epidermis (SkinEthic): a new model for screening skin-targeted androgen modulators
International Journal of Cosmetic Science, 22(6):397-407
BERNARD FX., BARRAULT C., DEGUERCY A., DE WEVER B. and ROSDY M. (2000)
SkinEthic Laboratories, rue Saint-Philippe 45, 06000 Nice, France.
Bioalternatives, Gençay, France.
The steroid 5-alpha-reductase isoenzymes (5-alphaR) transform testosterone into 17beta-hydroxy-5-alpha-androstan-3-one (5-dihydrotestosterone, DHT), which exerts a much stronger biological activity than does testosterone. Briefly, the two 5-alphaR isoenzymes are differentially expressed in the two major target organs of steroid action, the prostate (isoenzyme 2, 5-alphaR2) and the skin (isoenzyme 1, 5-alphaR1). 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 5-alphaR activity. The epidermal model was found to express the type-1 (skin) isoform of 5-alphaR and thus could be used as an enzyme source for the screening of 5-alphaR modulators for dermatological/cosmetic purposes. A reproducible and convenient assay method was developed, allowing both the evaluation of testosterone transformation into DHT (5-alphaR 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 5-alphaR.
The assay gave evidence of the inhibitory activity of finasteride against type-1 5-alphaR, 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 5-alphaR 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 5-alphaR1 at the transcriptional level.
© 2000 International Journal of Cosmetic Science.
KEYWORDS: 5α-reductase isoenzymes; Dihydrotestosterone; Reconstituted human epidermis; Screening model; Testosterone metabolism