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


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

Check out Bioalternatives’ updates and experience new testing ideas

  • Bioassays, models and services
  • Posts and publications
  • Events

Related Posts or publications

Pseudomonas aeruginosa flagellum is critical for invasion, cutaneous persistence and induction of inflammatory response of skin epidermis Pseudomonas aeruginosa, an opportunistic pathogen involved in skin and lung diseases, possesses numerous virulence factors, including type 2 and 3 secretion systems (T2SS and T3SS) and its flagellum, whose functions remain poorly known during cutaneo...
Acné vulgaris : Origines, symptômes et traitements actuels L’acné vulgaris est une maladie inflammatoire chronique cutanée qui touche la plupart des adolescents et concerne plus de la moitié des consultations en dermatologie. Cette pathologie, caractérisée par une hypersécrétion de sébum peut être à l’origin...
Acné vulgaris : Physiopathologie et mécanismes cellulaires L’acné vulgaris est une pathologie inflammatoire chronique cutanée localisée au niveau du follicule pilo-sébacé. Elle apparaît suite à une surproduction de sébum liée à des dysfonctionnements d’origine hormonale (androgène), environnementale (polluti...
La glande sébacée : Physiologie et fonctions La glande sébacée est un organe localisé au niveau du derme. Elle est responsable de la synthèse et de la sécrétion du sébum qui entre dans la composition du film hydrolipidique. Le rôle du sébum est de protéger la peau des agressions extérieures et ...
Interleukin-17A-induced production of acute serum amyloid A by keratinocytes contributes to psoriasis pathogenesis Acute-serum Amyloid A (A-SAA), one of the major acute-phase proteins, is mainly produced in the liver but extra-hepatic synthesis involving the skin has been reported. Its expression is regulated by the transcription factors NF-κB, C/EBPβ, STAT3 acti...