Spironolactone directly inhibits proliferation of cultured human facial sebocytes and acts antagonistically to testosterone and 5 alpha-dihydrotestosterone in vitro.
Akamatsu H; Zouboulis CC; Orfanos CE
Department of Dermatology, University Medical Center Steglitz, Free University of Berlin, Germany.
J Invest Dermatol, 1993 May, 100:5, 660-2
Spironolactone produces antiacne effects and has recently been shown to inhibit 5 alpha-dihydrotestosterone (5 alpha-DHT) receptors in human sebaceous glands. We applied spironolactone alone and combined with testosterone and 5 alpha-DHT to investigate its effects on the proliferation of human sebocyte cultures derived from facial skin. Secondary human facial sebocytes in 96-well culture plates were treated for 10 d by a single or combined application of testosterone (10(-8)-10(-5) M), 5 alpha-DHT (10(-8)-10(-5) M), and spironolactone (10(-12)-10(-7) M) in serum-free basal medium. Cell proliferation was assessed in six wells using a fluorometric assay. Testosterone and 5 alpha-DHT significantly stimulated sebocyte proliferation in a dose-dependent manner, the effect being strongest with 5 alpha-DHT. Spironolactone, on the other hand, caused a dose-dependent inhibition (25% and 50% at 10(-9) and 10(-7) M, respectively). Combined treatment of human facial sebocytes with spironolactone and testosterone or 5 alpha-DHT resulted in a lower proliferation than with androgens alone. The fact that spironolactone directly and dose dependently inhibits the proliferation of cultured human facial sebocytes and acts antagonistically to testosterone and 5 alpha-DHT at the cellular level is indicative of a receptor-mediated effect.
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