Role of Androgen in Mesenchymal Epithelial Interactions in Human Hair Follicle

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Human hair follicles, which are distributed in various and specific sites of the body, appear to have an inherited susceptibility for androgen-dependent growth. Beard, axillary, and frontal scalp dermal papilla cells (DPC) were recently shown to possess the characteristics of androgen target cells. These DPC show strong expression of androgen receptors, and the expression of type II 5alpha reductase is restricted to beard and frontal scalp DPC. These findings suggest that DPC mediate the signals of androgen to follicular epithelial cells in a paracrine fashion. We developed an in vitro co-culture system using DPC and keratinocytes (KC) to characterize the mode of androgen action in human hair follicles. Androgen significantly stimulated the proliferation of KC co-cultured with beard DPC, indicating that beard DPC produce androgen-dependent diffusible growth factors. Insulin-like growth factor-I was identified as one of the androgen-dependent paracrine growth factors produced by beard DPC. We also identified the inhibitory role of androgen on the growth of KC co-cultured with DPC from androgenetic alopecia (AGA) when the DPC were transfected with an expression vector encoding the androgen receptor. This growth suppression of KC was mediated by transforming growth factor-beta1 (TGF-beta1) derived from DPC of AGA, suggesting that TGF-beta1 is a paracrine mediator for AGA.