P5.48 Neurokinin 1 receptor ligands modulate human hair follicle cells responses and growth ex vivo

S. Lachgar, S.Metenier, S.Quibeuf, M. Charveron

European Research Center on Skin, IRPF, Hôtel-Dieu, Toulouse, France

It has been reported that neural mechanisms play a role in hair growth control. An induction of murine hair growth in vivo is obtained after treatment with substance P (SP).

In this study, we examined the expression of a SP receptor, neurokinin-1 (NK1-R) during: (a) the human hair cycle, (b) on isolated hair follicles, and (c) in cultured hair dermal papilla (HDPC). The impact of NK1-R ligands was assessed on the regulation of hair growth ex vivo in the presence or absence of two anti-hair loss molecules, minoxidil and neoruscogenin, which act on vascular targets. We used immunohistochemistry, Western–blot and RT-PCR analysis to examine NK1-R expression.

Human hair follicles and dermal papilla cells were isolated from the occipital region of the scalp and maintained in a defined medium.

Anagen hair follicles showed a strong expression of NK1-R in the dermal papilla and in the outer root sheath. A weak staining of NK1-R was restricted to hair follicle dermal papilla in the catagen and telogen stages.

Two isoforms of NKI-R protein corresponding to 44kDa and 54kDa were identified in cultured HDPC. A fragment of 640bp corresponding to NKI-R was obtained by RT-PCR. The nested PCR showed the expected band of NK1-R at 395bp.

HDPC’s treatment with SP increases the level of NKI-R gene and protein. The increase is stronger with NK1-R selective agonist [Sar9,Met (O2)11]-SP.

In human hair follicles ex vivo, we showed a significant dose–dependent stimulation of hair growth by SP and by NK1-R agonist. However, the NK1-R antagonist (L-732-138) inhibits hair follicle growth significantly.  SP potentiates the stimulatory effect of hair growth obtained in the presence of neoruscogenin or minoxidil

These results demonstrate a hair cycle-dependent expression of NK1-R and a differential modulation of hair growth in organ culture by NK1-R ligands. Following the potentiating effects of SP ex vivo, further studies in vivo should elucidate how two dual pathways (neural and vascular) act together in the control of hair growth.