[Pathomechanism of androgenetic alopecia and new treatment].
Hair follicles are composed primarily of epithelial and dermal components that develop from embryonic ectoderm and mesoderm respectively. The hair growth cycle is coordinated with complex processes that are dependent on the interactions of epithelial and dermal components. Beard and frontal scalp dermal papilla cells (DPCs) show the characteristics of androgen target cells. These DPCs expressed androgen receptor and type II 5alpha-reductase mRNA. To understand the mode of androgen action in human hair follicles, we developed an in vitro co-culture system using DPCs and follicular keratinocytes. Androgen significantly stimulated the proliferation of keratinocytes co-cultured with beard 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 from beard DPCs. On the other hand, we identified inhibitory roles of androgen on the growth of keratinocytes co-cultured with DPCs from human balding frontal scalp, when DPCs were transfected with the AR expression vector. This inhibitory effect was mediated by TGF-beta1 from the DPCs. Minoxidil and Finasteride were recently introduced for the treatment of androgenetic alopecia in Japan, and TGF-beta1 is the next target for innovative treatment.
Itami
Satoshi
S
Department of Dermatology, Course of Molecular Medicine, Graduate School of Medicine, Osaka University.
D000505:Alopecia / Q000188:drug therapy* / Q000209:etiology; D000728:Androgens / Q000502:physiology; D000818:Animals; D018920:Coculture Techniques; D018120:Finasteride / Q000627:therapeutic use*; D018859:Hair Follicle / Q000378:metabolism; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000502:physiology; D015603:Keratinocytes / Q000502:physiology; D008297:Male; D051379:Mice; D008914:Minoxidil / Q000627:therapeutic use*; D011944:Receptors, Androgen / Q000096:biosynthesis; D012867:Skin / Q000166:cytology / Q000378:metabolism
D000728:Androgens; D018970:Insulin-Like Growth Factor Binding Protein 1; D011944:Receptors, Androgen; D018120:Finasteride; D008914:Minoxidil