O#21   Stress-induced advanced catagen progression and increased homing of inflammatory cells into the vicinity of murine hair follicles is reduced by topical minoxidil

Petra Arck, Bori Handjiski, Eva M.J. Peters, Evelin Hagen, Burghard Klapp and Ralf Paus1. Dept of Internal Medicine, Humboldt University, Berlin, Germany; 1Dept of Dermatology, University of Hamburg, Germany

Stress has long been suspected as a possible cause of hair loss in various species, even though convincing experimental evidence has not been available. Recently, we have shown that sonic stress in fact alters hair growth in vivo in a murine model, and have postulated the existence of a "brain-hair follicle axis" (FASEB J, 13:2536-2538; 2001). In order to study whether a clinically available and widely used, topically active hair growth stimulator mitigates stress-triggered hair growth inhibition in a murine stress model, we have applied topical minoxidil in 5% solution. Female CBA/J mice were depilated and randomized in 2 groups, control (n=20) and stress (n=20). These groups were further divided into two subgroups and either treated daily with 5% minoxidil solution or vehicle alone. The stress group was exposed to sonic stress for 24 hours starting 14 days after anagen induction by depilation. All mice were sacrificed 16 days after depilation and assessed by standardized quantitative histomorphometry. Compared to non-stressed controls, all stressed mice showed an advanced progression towards catagen. This stress-triggered effect could be reduced by topical minoxidil treatment (p<0.001). Further, sonic stress significantly increased the number of hair follicles with apoptotic cells in the bulge and bulb region and inhibited intrafollicular keratinocyte proliferation (as measured by TUNEL/Ki67 immunostain). In addition, the number of clusters of perifollicular MHC class II+ cells (largely representing activated macrophages) and the number of degranulated perifollicular mast cells was significantly enhanced in the stressed mice. All of these stress-induced changes along the "brain-hair follicle axis" (apoptosis induction and inhibition of proliferation in the hair follicle, perifollicular inflammatory events) were downregulated by topical minoxidil application. We conclude that stress-induced hair growth-inhibition in mice can be effectively counteracted by topical minoxidil treatment.