Norepinephrine Regulates Keratinocyte Proliferation to Promote the Growth of Hair Follicles

Abstract

Psychological factors and stress can cause hair loss. The sympathetic-adrenal-medullary (SAM) axis has been reported to regulate the growth of hair follicles (HF). The sympathetic nerve is a component of the SAM axis, but it has not been sufficiently or convincingly linked to hair growth. In this study, we demonstrate that chemical sympathectomy via administration of the neurotoxin 6-hydroxydopamine (6-OHDA) to mice inhibited HF growth, but treatment with the β-adrenoceptor antagonist propranolol (PR) had no effect. HF length and skin thickness were greater in PR-treated and control mice than in 6-OHDA-treated mice, as evidenced by hematoxylin and eosin staining. Furthermore, we found that the reduced HF growth in sympathectomized animals was accompanied by a decreased keratinocyte proliferation. Moreover, the neurotransmitter norepinephrine (NE) was found to efficiently promote HF growth in an organotypic skin culture model. Together, these findings suggest that sympathetic nerves regulate keratinocyte behaviors to promote hair growth, providing novel insights into stress-related, chemotherapy-, and radiotherapy-induced alopecia.