Effect of 5α-Dihydrotestosterone and Testosterone on Apoptosis in Human Dermal Papilla Cells

Abstract

Pathogenetic mechanisms in androgenetic alopecia are not yet fully understood; however, it is commonly accepted that androgens like testosterone (T) and 5α-dihydrotestosterone (5α-DHT) inhibit hair follicle activity with early induction of the catagen. Thus, we investigated the influence of T and 5α-DHT on proliferation, cell death and bcl-2/bax expression in cultured dermal papilla cells (DPC) from nonbalding scalp regions of healthy volunteers. T and 5α-DHT induced apoptosis in DPC in a dose-dependent and time-related manner; in addition a necrotic effect due to T at 10^–5 M was found. Interestingly, bcl-2 protein expression was decreased in T- and 5α-DHT-treated cells, leading to an increase in the bax/bcl-2 ratio. In addition, T and 5α-DHT induced proteolytic cleavage of caspase 8 and inhibited proliferation of DPC at 10^–5 M. High concentrations of T and 5α-DHT were needed to induce apoptotic effects in DPC. These data suggest that DPC from nonbalding scalp regions do have the capacity to undergo apoptosis, but need a high androgen stimulus. The present study provides an interesting new pathogenetic approach in androgenetic alopecia.