Ultraviolet B Irradiation of the Eye Activates a Nitric Oxide-dependent Hypothalamopituitary Proopiomelanocortin Pathway and Modulates Functions of α-Melanocyte-stimulating Hormone-responsive Cells

Abstract

Ultraviolet B radiation increases DOPA-positive melanocytes in the skin specifically at the site of exposure. We found unexpectedly that ultraviolet B irradiation of the eye increased the concentration of alpha-melanocyte-stimulating hormone in plasma and systemically stimulated epidermal melanocytes in mice. To test the possible involvement of hypothalamopituitary proopiomelanocortin system in the systemic activation of skin melanocytes, ultraviolet B was also irradiated to the eye after hypophysectomy. Hypophysectomy strongly inhibited the ultraviolet B-induced stimulation of melanocytes. To elucidate the pathway by which ultraviolet B irradiation of the eye activated the hypothalamopituitary system, we examined the effect of bilateral ciliary ganglionectomy and denervation of the optic nerves on the ultraviolet B-induced melanocyte stimulation. Ciliary ganglionectomy, but not optic nerve denervation, strongly inhibited melanocyte stimulation by localized irradiation of the eye. Furthermore, melanocyte stimulation by localized ultraviolet B irradiation of the eye was not observed in mice that lack the inducible type of nitric oxide synthase. These results clearly indicate that a signal evoked by ultraviolet B irradiation of the eye is transmitted in a nitric oxide-dependent manner through the ciliary ganglia involving the first branch of the trigeminal nerve to the hypothalamopituitary proopiomelanocortin system, resulting in upregulation of alpha-melanocyte-stimulating hormone secretion and consequent stimulation of melanocytes in the skin. The novel network involving the trigeminal nerve and nitric oxide-dependent signaling pathway might play important parts in the activation of proopiomelanocortin-dependent biologic reactions, such as alpha-melanocyte-stimulating hormone-induced stimulation of melanocytes in the skin, in ultraviolet B-enriched environments.

Coat color determination by miR-137 mediated down-regulation of microphthalmia-associated transcription factor in a mouse model

“…Mutations of MC1R gene in many species, including humans, can cause the phenotype of red hair (Goding 2007). Recently, Keiichi Hiramoto used UV B radiation to stimulate the eyes and ears of mice and revealed the nitric oxide (NO)-dependent signaling of cellular response in activating the hypothalamopituitary proopiomelanocortin system, thereby enhancing the hypophysial secretion of a-MSH to stimulate a-MSH-receptorresponsive cells (Hiramoto et al 2003). The expression of MC1R induced a-MSH and enhanced the ability of melanocytes to response to melanogensis (Ortonne 2002).…”

Evidence for phenotypic plasticity in response to photic cues and the connection with genes of risk in schizophrenia

“…In contrast to most other animals, humans have a large cutaneous surface area that is responds to sunlight by proportional (not step-wise) adjustments to sunlight intensity for both vitamin D (Chen et al, 2007) and melanotropin production (Farooqui et al, 1993; Chakraborty et al, 1996; Hiramoto et al, 2003). …”

Prevention of the Ultraviolet B-Mediated Skin Photoaging by a Nuclear Factor κB Inhibitor, Parthenolide

“…The melanocyte count in skin tissues was determined microscopically according to the method of Hiramoto et al (2003). The cartilages were manually removed from the excised mouse ear specimen, and the skin tissues were soaked in 2 N NaBr solution at 37°C for 2 h. The epidermal and basal layers were exfoliated from rest of the skin tissue by this procedure, and melanocytes were stained by immersing in 0.1 M phosphate-buffered saline (pH 7.2) containing 0.14% L-DOPA at room temperature for 3 h and counted under a microscope.…”