L-18   HORMONAL EFFECTS ON DERMAL PAPILLA CELLS AND HAIR GROWTH

VA Randall University of Bradford, Bradford, UK.

Androgens are major regulators of human hair growth with markedly different effects on hair growth depending on body site. They stimulate vellus follicles to produce terminal hairs in the pubic and axillary regions of both sexes during puberty, and the higher adult male levels promote greater terminal hair on the face, chest, legs etc. In contrast, they can cause the reverse transformation on the scalp in genetically predisposed individuals leading to male pattern baldness or have no effect e.g. on the eyelashes. The mesenchyme-derived dermal papilla located at the base of the mainly epithelial hair follicle controls many aspects of hair growth including the type of hair produced by a follicle. It is also believed to be the site of androgen action in the hair follicle with androgens altering the production of paracrine factors and/or extracellular matrix components which regulate other follicle cells indirectly. Dermal papilla cells have been cultured successfully from follicles from a range of species and retain their follicle inductive capacity for several passages suggesting that they would be a good model system for studying androgen action in human follicles. Since androgens act via intracellular androgen receptors, a pre-requisite for an androgen target organ would be the presence of androgen receptors. Dermal papilla cells from androgen sensitive sites including human beard and balding follicles and red deer mane do contain specific, saturable androgen receptors in higher numbers than those from non-androgen-dependent human scalp or red deer flank follicles. Interestingly, cells from the follicular dermal sheath which is able to replace the dermal papilla in vivo and induce new follicle formation, from androgen-dependent sites also contain androgen receptors. This means that if dermal sheath is used to induce new follicles in future, they may well retain the androgen responsiveness of their parent follicle. Metabolism of the major male circulating androgen, testosterone, to its more potent form, 5alpha-dihydrotestosterone, is required for hair growth in many male-specific areas as demonstrated by men with 5alpha-reductase deficiency. Testosterone metabolism by dermal papilla cells in vitro mirrors this pattern with little metabolism by pubic and axillary follicles but significant amounts in beard cells. Dermal papilla cells also secrete soluble mitogenic factors in culture which stimulate the growth of keratinocytes, outer root sheath cells and other dermal papilla cells. Importantly, androgens in vitro alter the amount produced by androgen-sensitive cells in line with their response in vitro. These results strongly supports the role of the dermal papilla in androgen action in hair follicles. Current attention is focussed on identifying these regulatory factors. Mitogenic factors also act across the species barrier and inhibit rodent hair growth in vivo. Further studies of androgen action in cultured dermal papilla cells should provide increased understanding of androgen action in human hair follicles leading to better treatments for androgen-dependent disorders.