Androgen action on human skin – from basic research to clinical significance

Androgens affect several functions of the human skin, such as sebaceous gland growth and differentiation, hair growth, epidermal barrier homeostasis and wound healing. Their effects are mediated by binding to nuclear androgen receptors. Androgen activation and deactivation are mainly intracellular events. They differ from cell type to cell type and between cells at different locations. The major circulating androgens, dehydroepiandrosterone sulfate and androstenedione, are predominantly produced in the adrenal glands, and testosterone and 5alpha-dihydrotestosterone are mainly synthesized in the gonads. Testosterone in women and 5alpha-dihydrotestosterone in both genders are also synthesized in the skin. Skin cells express all androgen metabolizing enzymes required for the independent cutaneous synthesis of androgens and the development of hyperandrogenism-associated conditions and diseases, such as seborrhea, acne, hirsutism and androgenetic alopecia. The major thrust of drug design for the treatment of androgen-associated disorders has been directed against several levels of androgen function and metabolism. Partial effectiveness has only been achieved either by androgen depletion, inhibition of androgen metabolism or blockade of the androgen receptor.