097 Expression of ErbB Protooncogene family members in human hair follicle epithelium correlates with the catagen inductive capacities of heregulin ß1.

EMJ Peters, F Löhr, C Kuwert, I Moll, R Paus. Department of Dermatology, University Hospital Eppendorf, University of Hamburg, Hamburg, Germany

Activation of growth and differentiation cascades by growth factors such as EGF, and heregulin play important roles in hair growth control. Their cognate subtype I receptor tyrosine kinases erbB-2, erbB-3, and erbB-4 are known to play a major role in epithelial growth control, with erbB-2 enhancing signalling through erbB-3 and erbB-4, which promotes epithelial proliferation. However, in the absence of erbB-2, erbB-3 and erbB-4 appear to promote differentiation. Since, EGF and erbB-2 transgenic mice display distinct hair growth abnormalities, we have further explored the role of the erbB protooncogene family in hair biology. We employed immunohistochemistry to detect erbB-2, erbB-3, and erbB-4 in human scalp skin samples. In anagen hair follicles, we found predominant staining for all investigated receptors in the proximal outer root sheath and the sebaceous gland, but never in the dermal papilla. ErbBs were also immunoreactive in cells of the keratogeneous zone. Additional ErbB-2 immunoreactivity was seen in matrix cells, while erbB-4 was detected distal of the keratinogeneous zone. Telogen hair follicles exhibited only very weak epithelial staining for all three markers. Epidermal expression was high for erbB-2, erbB-3, and erbB-4 in the basal layer but weak in suprabasal layers for erbB-2. In addition, cultured human anagen hair follicles (Philpott model) were treated with heregulin ß1, a high affinity ligand for erbB-3 and erbB-4. Treatment of human anagen VI scalp hair follicles with 0,5µg/ml heregulin ß1 resulted in inhibition hair shaft elongation (more than 35 % compared to untreated controls), and premature induction of a catagenlike stage in the majority of the cultured hair follicles. These delete suggest a role for erbB-3 and erbB-4- mediated signaling as a stimulus for trichocyte differentiation processes, e.g. in the regressing outer root sheath during catagen. Therefore, erbB-signaling is an attractive new target for therapeutic control in human hair growth. ErbB-3 or erbB-4 agonists may lead to development of new pharmaceutical tools to manipulate hair growth e.g. in hirsutism.