Androgens affect the activity of human sebocytes in culture in a manner dependent on the localization of the sebaceous glands and their effect is antagonized by spironolactone.
To investigate the varying response of the pilosebaceous unit to androgens functional studies were performed on the effects of testosterone and 5 alpha-dihydrotestosterone on cultured human sebocytes derived from different skin regions. In addition, the effect of spironolactone on the proliferation of androgen-stimulated human sebocytes derived from facial skin was evaluated. Testosterone (10(-11) to 10(-5) M), 5 alpha-dihydrotestosterone (10(-11) to 10(-5) M) and spironolactone (10(-12) to 10(-7) M) were added for 10 days as single substances or in combinations to human sebocytes in secondary culture maintained in a serum-free medium. Cell proliferation was assessed using a fluorometric assay. Intracellular lipids were extracted from sebocytes treated with androgens (10(-7) M) for 10 days after confluency. Testosterone inhibited the proliferation of sebocytes derived from the legs with a 50%-inhibitory concentration at 10(-5) M and induced a 50% decrease of intracellular lipids. In contrast, 5 alpha-dihydrotestosterone stimulated the activity of leg sebocytes with a 50% increase of proliferation at 10(-5) M, and a 175% increase of intracellular lipids. On the other hand, the proliferation of facial sebocytes was significantly stimulated by testosterone with a 50%-stimulatory concentration at 10(-6) to 10(-5) M and mostly by 5 alpha-dihydrotestosterone with a 50% enhancement at 10(-8) to 10(-7) M. Spironolactone inhibited the proliferation of facial sebocytes in a dose-dependent manner with a 25%-inhibitory concentration at 10(-9) M. Simultaneous treatment of facial sebocytes with spironolactone and testosterone or 5 alpha-dihydrotestosterone resulted in decreased proliferation when compared to the growth obtained under androgens alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Zouboulis
C C
CC
Department of Dermatology, University Medical Center Steglitz, Free University of Berlin, FRG.
Akamatsu
H
H
Stephanek
K
K
Orfanos
C E
CE
D000328:Adult; D000726:Androgen Antagonists / Q000494:pharmacology*; D000728:Androgens / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000378:metabolism; D005145:Face; D005260:Female; D006801:Humans; D007866:Leg; D008297:Male; D012627:Sebaceous Glands / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013148:Spironolactone / Q000494:pharmacology*; D013739:Testosterone / Q000378:metabolism
D000726:Androgen Antagonists; D000728:Androgens; D013196:Dihydrotestosterone; D013148:Spironolactone; D013739:Testosterone