Original	Horm Metab Res 2007; 39: 141-148 DOI: 10.1055/s-2007-961814
© Georg Thieme Verlag KG Stuttgart · New York
Inhibition of 5α-Reductase Activity in SZ95 Sebocytes and HaCaT Keratinocytes In Vitro
K. Seiffert1, H. Seltmann2, M. Fritsch3, C. C. Zouboulis2,4
1Division of Dermatology and Cutaneous Sciences, Michigan State University, East Lansing MI, USA 2Laboratory of Biogerontology, Dermato-Pharmacology, and Dermato-Endocrinology, Institute of Clinical Pharmacology and Toxicology, Charité Universitaetsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany 3Schering Research Laboratories, Schering AG, Berlin, Germany 4Departments of Dermatology and Immunology, Dessau Medical Center, Dessau, Germany

Abstract

Inhibition of 5α-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 5α-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 5α-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 5α-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 5α-dihydrotestosterone-induced sebocyte proliferation. Our experimental findings and the existing clinical results indicate that the inhibition of 5α-reductase activity alone may be insufficient to reduce overall sebocyte activity and improve acne lesions.

Keywords

androgens - anti-androgens - 5α-reductase inhibitors - sebaceous gland - keratinocytes - cell proliferation - acne