Inhibition of 5α-Reductase Activity in SZ95 Sebocytes and HaCaT Keratinocytes In Vitro

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

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1 The work was performed at the Department of Dermatology, University Medical Center Benjamin Franklin, Freie Universitaet Berlin, Berlin, Germany

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