Regulation of human hair follicle growth by neurokinin-1 receptor ligands

Recent reports revealed that neural mechanisms play a role in hair growth control. An induction of murine hair growth is obtained after treatment with substance P (SP). In this study, we examined the expression of a SP receptor: the neurokinin-1 (NK1-R) during: 1) the human hair cycle, 2) on isolated hair follicle, and 3) in cultured hair dermal papilla (HDPC) and the impact of NK1-R ligands on the regulation of hair growth. We used immunohistochemistry, Western blot and RT-PCR analysis to examine its expression. Anagen hair follicles showed a strong expression of NK1-R in dermal papilla and in the outer root sheath. Weak expression of NK1-R was observed in hair follicle at the catagen and telogen stages. Two isoforms of NK1-R protein corresponding to 44 kDa and 54 kDa were identified in cultured HDPC. A fragment of 640 bp corresponding to NK1-R was obtained by RT-PCR. The nested PCR showed the expected band of NK1-R at 395 bp. HDPC treatment with SP increases the level of NK1-R gene and protein. The increase is stronger with NK1-R-selective agonist [Sar9, Met (O2) 11]-SP. Ex vivo studies showed a significant dose-dependent stimulation of hair growth by SP and by NK1-R agonist. However, the NK1-R antagonist (L-732–138). showed a significant inhibition of hair follicle growth. These results demonstrate the presence of NK1-R in the growing human hair follicle. NK1-R is activated by SP and NK1-R agonist. Ex vivo studies indicate that NK1-R antagonist inhibited hair follicle growth.