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.

Recent Progress in the Understanding of the Effect of Sympathetic Nerves on Hair Follicle Growth

“…After using guanidine to selectively deplete the NE reserve of sympathetic nerves endings, hair growth was inhibited. Then, the cycle does not recover until the adrenaline level is restored (Kong et al, 2015).…”

Gene expression profile of human follicle dermal papilla cells in response to Camellia japonica phytoplacenta extract

“…Two upregulated genes, ADCY4 and ADRA2A , are known as major receptors targeted by epinephrine and norepinephrine (WP4589). A recent study showed that keratinocyte proliferation is regulated by the norepinephrine hormone to promote hair follicle growth [51]. Therefore, ADRA2A encoding adrenoceptor alpha 2A might be involved in hair follicle growth by interacting with norepinephrine.…”

An increase in normetanephrine in hair follicles of acne lesions through the sympatho‐adrenal medullary system in acne patients with anxiety

“…Previous studies have shown that sympathetic nerves participate in the regulation of hair follicle growth in mice. 12,13 Given that psychological stress causes noradrenaline secretion to salivary glands, 4,6 noradrenaline might exist in hair follicles through the SAM system in response to psychological stress. In the present study, the normetanephrine in acne lesions positively related to STAI-S and was significantly detectable in acne patients with high rather than low anxiety.…”