Sebocytes Are the Key Regulators of Androgen Homeostasis in Human Skin

The study investigated the expression and activity of androgen receptor and androgen metabolizing enzymes in three human skin cell populations: SZ95 sebocytes, HaCaT keratinocytes, and MeWo melanoma cells. It was found that androgen receptor mRNA was present in SZ95 sebocytes and HaCaT keratinocytes but not in MeWo melanoma cells. SZ95 sebocytes were unique in expressing 3beta-hydroxysteroid dehydrogenase/Delta(5-4)-isomerase isotype 1 mRNA and its metabolic activity, which could be inhibited by cyproterone acetate. All three cell types expressed type 2 17beta-hydroxysteroid dehydrogenase, type 1 5alpha-reductase, and 3alpha-hydroxysteroid dehydrogenase mRNA, but only SZ95 sebocytes expressed type 3 17beta-hydroxysteroid dehydrogenase mRNA. Testosterone was primarily metabolized to androstenedione and then to 5alpha-androstanedione, with the type 1 5alpha-reductase inhibitor effectively inhibiting this process. 5alpha-androstanedione was further degraded to androsterone, with HaCaT keratinocytes showing stronger activity than SZ95 sebocytes. The study concluded that sebocytes and keratinocytes have distinct roles in androgen metabolism, with sebocytes synthesizing and inactivating testosterone to maintain homeostasis, while keratinocytes are more involved in androgen degradation.