The role of androgen and androgen receptor in skin-related disorders

Abstract

Androgen and androgen receptor (AR) may play important roles in several skin-related diseases, such as androgenetic alopecia and acne vulgaris. Current treatments for these androgen/AR-involved diseases, which target the synthesis of androgens or prevent its binding to AR, can cause significant adverse side effects. Based on the recent studies using AR knockout mice, it has been suggested that AR and androgens play distinct roles in the skin pathogenesis, and AR seems to be a better target than androgens for the treatment of these skin diseases. Here, we review recent studies of androgen/AR roles in several skin-related disorders, including acne vulgaris, androgenetic alopecia and hirsutism, as well as cutaneous wound healing.

Fig. 1

ASC-J9® treatment alleviates seborrhea symptoms in male fuzzy rats. Starting from 28 days of age, male fuzzy rats were separated into 3 groups. One group was castrated (Cas), another was treated topically with ASC-J9® cream on the dorsal skin 5 days a week (ASC-J9®), and the other group was left untreated (Non). (A) Eight weeks after castration or ASC-J9® treatment, the dorsal skin was photographed to compare the seborrhea between groups. (B) The skin tissues were dissected and treated with 17 mM EDTA/PBS buffer for 2 hours at 37°C. Then the epidermis was separated from the dermis by forceps and fixed with 4% paraformaldehyde/PBS solution. The sebaceous glands were observed under a dissecting microscope at a magnification of 50X and photographed. Circles indicate the sebaceous ducts, and (C) the diameter of the ducts was measured using Image J software (NIH). Data are presented as mean ± S.E. *, p<0.01

Fig. 2

The role of androgens/AR in acne formation/progression. Acne formation in human results from excessive sebum formation and is usually accompanied by excessive inflammation and infections in the hair follicle. Macrophages and neutrophils are recruited to the inflamed follicles and secrete cytokines and other mediators to promote the inflammation and infection clearance. However the inflammatory response also damages the normal tissues in the follicles. AR can promote the inflammatory response mediated by macrophages and neutrophils, and androgens/AR can also directly promote sebum production that plugs the follicle pore. The IGF-1/FOXO1 pathway can enhance AR activity and subsequently promote sebum production. Current treatments for acne include antibiotics for infection clearance and therefore reducing the subsequent inflammation. Some antibiotics (eg. tetracycline) possess both antimicrobial and anti-inflammatory effects. Retinoid (and its derivatives, eg. isotretinoin) suppresses sebum production and promotes extrusion of the plugged material in the follicles. Antiandrogens reduce androgen levels, and AR degradation enhancers (ADEs) directly target AR to regulate the AR-mediated activities during acne formation/progression, such as reducing sebum production and suppressing the function of macrophages and neutrophils to dampen the inflammatory response.