S1 ANDROGEN METABOLISM AND HOW IT AFFECTS HAIR GROWTH
Randall VA
Department of Biomedical Sciences, University of Bradford, UNITED KINGDOM

Changes in hair growth patterns distinguish adults from children and men from women. This important role in social and sexual communication means that hair growth disorders such as hirsutism and androgenetic alopecia frequently cause psychological distress. Androgens are known to stimulate these changes, but how they act in the follicle is not fully understood. Androgens transform vellus follicles, producing tiny, colorless hairs, into terminal ones forming larger, more pigmented hairs in many areas e.g. pubis and axilla in both sexes, while causing the reverse on the scalp leading to balding. Therefore, the mechanisms for their different responses must lie within the follicle itself. A range of androgens circulates in the blood, which can be metabolised to more, or less, potent forms or even estrogens. The most potent androgen found in large amounts in the male, testosterone, can act via intracellular androgen receptors as itself, or after metabolism to 5a-dihydrotestosterone, or via oestrogen receptors after aromatisation to 17b-oestradiol; recent suggestions include a mechanism independent of steroid hormone receptors. Various human genetic abnormalities reveal important information about how androgens act in hair follicles. Genetic males with complete androgen insensitivity, i.e. without functional androgen receptors, have a female phenotype despite high levels of androgens; however, they do not develop even pubic or axillary hair. This demonstrates that androgens act in follicles via androgen receptors. In men with 5a-reductase deficiency, i.e. lacking an enzyme that metabolises testosterone to 5a-dihydrotestosterone, hair growth resembles the female pattern. This suggests that the isoenzyme, 5a-reductase type 2, is necessary to metabolise testosterone to 5a-dihydrotestosterone in male characteristic follicles such as beard and chest follicles. Individuals with 5a-reductase deficiency do not go bald and finasteride, a 5a-reductase type 2 inhibitor, prevents, or reverses, androgenetic alopecia suggesting that this metabolism is also necessary for in androgenetic alopecia. All individuals with 5a-reductase deficiency to date have had difficulties with the type 2 isoenzyme; type 1 deficiency has not been described so its role in hair growth remains unclear. Studies using dermal papilla cells derived from hair follicles with varying responses to androgens in vivo have demonstrated similar patterns of testosterone metabolism in vitro; beard cells rapidly metabolised testosterone to 5a-dihydrotestosterone, while pubic and axillary cells did not. These results strongly support a mechanism of action in the hair follicle where androgens act on the hair follicle cells via the regulatory mesenchyme-derived dermal papilla at the base of the hair follicle.