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
Correspondence
C. C. Zouboulis
Departments of Dermatology and Immunology
Dessau Medical Center
Dessau
Germany
Phone: +49/340/501 40 00
Fax: +49/340/501 40 25
Email: christos.zouboulis@klinikum-dessau.de