A NEW ROLE FOR NEUROTROPHIN-3 - INVOLVEMENT IN THE REGULATION OF HAIRFOLLICLE REGRESSION (CATAGEN)

Nervous system and hair follicle epithelium share a common ectodermal origin, and some neurotrophins (NTs) can modulate keratinocyte prolife ration and apoptosis, Therefore, it is reasonable to ask whether NTs a re also involved in hair growth control. Here, we show that the expres sion of NT-3 and its high-affinity receptor, tyrosine kinase C, in the skin of C57BL/6 mice is strikingly hair cycle-dependent, with maximal transcript and protein expression seen during spontaneous hair follic le regression (catagen), During catagen, NT-3 and tyrosine kinase C ar e coexpressed by terminal deoxynucleotidyl transferase mediated ill si tu nick end labeling-positive keratinocytes in the club hair and secon dary germ. NT-3-overexpressing transgenic mice show precocious catagen development during the postnatal initiation of hair follicle cycling, whereas heterozygous NT-3 knockout (+/-) mice display a significant c atagen retardation. Finally, NT-3 stimulates catagen development in or gan culture of normal C57BL/6 mouse skin. These observations suggest t hat the hair follicle is both a source and target of NT-3 and that NT- 3/tyrosine kinase C signaling is functionally important in the control of hair follicle regression. Therefore, tyrosine kinase C agonists an d antagonists deserve systematic exploration for the management of hai r growth disorders that are related to premature (alopecia/effluvium) or retarded catagen (hirsutism/hypertrichosis).