ABSTRACT
Minoxidil induces hair growth in male pattern baldness and prolongs the anagen phase. All-trans retinoic acid (ATRA) has been reported to act synergistically with minoxidil in vivo: they can enhance more dense hair regrowth than either compound alone. We evaluated the effect of minoxidil combined with ATRA on hair growth in vitro. The effect of co-treatment of minoxidil and ATRA on hair growth was studied in hair follicle organ culture. In cultured human dermal papilla cells (DPCs) and normal human epidermal keratinocytes, the expressions of Erk, Akt, Bcl-2, Bax, P53 and P21 were evaluated by immunoblot analysis. Minoxidil plus ATRA additively promoted hair growth in vitro, compared with minoxidil alone. In addition, minoxidil plus ATRA elevated phosphorylated Erk, phosphorylated Akt and the ratio of Bcl-2/Bax, but decreased the expressions of P53 and P21 more effectively than by minoxidil alone. Our results suggest that minoxidil plus ATRA would additively enhance hair growth by mediating dual functions: 1) the prolongation of cell survival by activating the Erk and Akt signaling pathways, and 2) the prevention of apoptosis of DPCs and epithelial cells by increasing the ratio of Bcl-2/Bax and downregulating the expressions of P53 and P21.
Subject(s)
Humans , Tretinoin/administration & dosage , Minoxidil/administration & dosage , Keratolytic Agents/administration & dosage , Hair/cytology , Drug Combinations , Dose-Response Relationship, Drug , Cells, Cultured , Cell Proliferation/drug effectsABSTRACT
BACKGROUND: The immunological characteristics of human hair follicles with the hair growth cycle have not yet been fully elucidated. It is suggested that expressional changes of the immunological markers in the hair cycle may play a role in catagen induction of the hair follicles. OBJECTIVE: To analyze the immunological features in human hair follicles according to the hair growth cycle. METHODS: An immunohistochemical study was performed on frozen sections of human hair follicles using major histocompatibility complex (MHC) class I & II, CD1a, Fas, Fas ligand, and ACTH antibodies. We then compared the hair cycle-associated expressional changes of these markers. RESULTS: Human anagen hair bulbs showed very low level of the MHC class I expression. In catagen transition, enhanced expression of the MHC class I was observed in the proximal hair follicles. This change may correspond to regressing morphological change of hair follicles in the catagen transition. Some changes in the expression of MHC class II and Fas/FasL in hair follicles were also observed in catagen transition. CONCLUSION: Downregulation of MHC class I expression in the proximal epithelium of the anagen hair bulb may contribute to so-called 'immune privilege'. In catagen transition, the expression of MHC class II and Fas/FasL, together with upregulation of MHC class I, might be related to morphologic changes of the hair follicle.