080 Endothelins Induce the Regression of Anagen Hair Follicle via Endothelin Receptors

N. Tsuji, A. Ohuchi, S. Moriwaki, Y. Takema. Biological Science Laboratories, Kao Corp., Tochigi, Japan

It has been reported that the several peptide or cytokines (EGF, TGFâ etc.) suppress hair growth in vivo. We have found the interesting phenomenon that subcutaneous injection of endothelins induces morphological transition of hair follicle at an anagen phase into a catagen-like appearance in guinea pig. In this study, we examined the mechanism of hair regression induced by endothelins in in vivo and in vitro study. Histological examination revealed that the catagen-like morphological change of anagen hair follicles caused one day after subcutaneous injection of endothelins (0.3µg/50µl) into the dorsal skin of guinea pig, and anagen hair follicles were completely disappeared associated with depilation four days after endothelin injection. The depilation by endothelin-1 was significantly inhibited by the simultaneous injection of endothelin receptor antagonist, PD142893 (10µg). The topical application of endothelin-1 (0.02% in polyethylene glycol) significantly inhibited hair re-growth of C3H mice. In order to examine whether endothelins would directly act on hair follicle, the isolated human hair follicles were maintained in serumfree Williams E medium with or without endothelin-1. The rate of elongation and DNA synthesis of hair follicle was significantly suppressed by the addition of endothelin-1 at a dose of 100ng/ml. And the hair follicles incubated with endothelin-1 changed morphologically to a club hair-like structure. These results strongly suggested that endothelins would directly induce the regression of growing hair follicles via endothelin receptors on follicular cells.