038 Principles of hair follicle cycling

Ralf Paus, Dept. of Dermatology, University Hospital Hamburg-Eppendorf, University of Hamburg, D-20246 Hamburg, Germany

The hair follicle (HF) is the only mammalian organ that permanently undergoes cyclic transformations from long stages of growth (anagen), via rapid, organ involution driven by programmed keratinocyte death (catagen) to a stage of relative quiescence (telogen). In addition, extrusion of the hair shaft may represent a fourth, independently regulated hair cycle phase (exogen). The HF may exit from cycling only by entering into “programmed organ death”, which may be a physiological programme for the deletion of malfunctioning follicles, or of follicles that have exhausted the number of cycles they can traverse. HF cycling begins with the first entry into catagen, immediately after the completion of HF morphogenesis. The first hair cycle in both man and in rodents is synchronized, and only subsequent cycles become desynchronized. Thus, the basic regulation of HF cycling is likely to follow the same fundamental regulatory controls in all mammalian species, irrespective of the fact that there are profound differences in the hair cyle-modulatory effects e.g. of steroid hormones and growth factors between species and defined hair follicle-subpopulations. The molecular nature and organisation of the autonomous “hair cycle clock” (HCC) that dictates HF cycling and is located in the skin itself is still unkown. The HCC exploits controlled switches in the local epithelial-mesenchymal signalling milieu of growth factors, cytokines, hormones, neuropeptides and adhesion moelcules as well as in the expression of cognate receptors form the basis of the HCC, with an intriguing predominance of hair growth-inhibitors over stimulatory signals. Basic criteria that any convincing HCC theory should meet are defined, and several previously proposed theoretical concepts that attempt to explain the HCC are critically discussed. In this context, possible analogies between the molecular controls of hair follicle induction/morphogenesis and cycling will be critically discucced. Finally, various chronobiological devices that the hair follicle employs during its development and cycling are distinguished, and their clinical relevance is explored.