L-17   ANDROGENS ACTION IN HUMAN HAIR FOLLICLES

S. Itami. Osaka University School of Medicine, Osaka, Japan.

Hair growth cycle is coordinated and complex processes that are dependent on the interactions of epithelial and dermal components. Although the precise mechanism of hair growth regulation by the hormone is yet to be established, beard, axillary and frontal scalp dermal papilla cells (DPCs) possess the characteristics of androgen target cells. Beard, and frontal scalp DPCs expressed androgen receptor (AR) and type II 5alpha-reductase mRNA. In order to know the mode of androgen action in human hair follicles, we developed an in vitro coculture system using human dermal papilla cells (DPCs) and outer root sheath cells. Androgen significantly stimulated the proliferation of outer root sheath cells cocultured with beard or axillary DPCs, suggesting that these DPCs produce androgen-dependent diffusible growth factors. Insulin-like growth factor-I (IGF-I) was identified as one of the androgen dependent paracrine growth factors in beard DPC. Although androgen stimulates the beard growth, it paradoxically suppresses the growth of frontal scalp hair of androgenetic alopecia in vivo. We attempted establishing an in vitro coculture system using DPCs from androgenetic alopecia (AGA) and keratinocytes (KCs) to explore the pathomechanism of AGA. Since the expressions of mRNA of AR decreased during subcultivation of DPCs in vitro, we transiently transfected the AR expression vector into the DPCs and cocultured them with KCs. In this modified coculture, androgen significantly suppressed the growth of KCs, indicating that overexpression of AR can restore the responsiveness of the DPCs to androgen in vivo. We found that androgen up-regulated the expression of TGF-beta mRNA in the cocultured DPCs. Androgen stimulated the secretion of both total and active TGF-_1 in the conditioned medium, suggesting that activation process of TGF-beta is also involved in the androgen-induced suppression of epithelial cell growth. We proposed that this modified coculture system is a powerful in vitro model to elucidate the pathomechanism of androgenetic alopecia.