Regulation of <i>α</i>-Melanocyte-Stimulating Hormone by Testosterone Is Associated with the Onset of Atopic Dermatitis Symptoms during Exercise

Objective: Atopic dermatitis (AD) symptoms are altered with exercise. However, no study has investigated the association between testosterone and AD. The aim of this study was to investigate the role of testosterone by which the strength and weakness of exercise affects the skin symptoms of AD. Methods: Specific pathogen-free (SPF) and conventional NC/Nga mice were used. NC/Nga mice spontaneously developed dermal symptoms similar to AD patients. Two exercises, mild (20 m/min, 60 min) and rigorous (25 m/min, 90 min), were carried out using a treadmill four times every alternate day. Furthermore, we administered testosterone (0, 5, 50, 500, and 5000 pg/mice) to non-exercised conventional NC/Nga mice. On the final day of this experiment, we analyzed the plasma levels of immunoglobulin E (IgE), interleukin (IL)-6, IL-4, IL-13, testosterone and α-melanocyte-stimulating hormone (α-MSH) by ELISA kit. Results: Symptoms manifested by NC/Nga mice were strongly exacerbated upon severe exercise but were ameliorated during mild exercise. Between mild and severe exercised conventional mice, the plasma level of IgE was not changed. On administering an equivalent amount of testosterone, depending on the exercise, AD-like symptoms in non-exercising NC/Nga mice were ameliorated with mild exercise and exacerbated through rigorous exercise. Plasma IL-6, IL-4, and IL-13 levels remained unchanged between +50 pg (mild) and +500 pg (severe) testosterone administration. Plasma α-MSH levels were elevated with +500 pg testosterone but decreased with +50 pg testosterone administration. Conclusion: The present results suggest that exercise largely mimics AD symptoms depending on the α-MSH and testosterone levels.

<i>Momordica charantia</i>Ameliorates Atopic Dermatitis by Inhibiting the Expression of Inducible Nitric Oxidase Synthase in NC/Nga Mice

Introduction: Momordica charantia (MC) has been reported to possess various beneficial effects. Improvement in natural aging of the skin has been observed with the use of MC. However, few studies have detailed the effects of MC on atopic dermatitis (AD). Therefore, in this study, we investigated the effects of MC on the skin symptoms of AD. Methods: Specific pathogen-free and conventional NC/Nga mice were orally administered a 50 mg/kg/day dose of MC every day for 2 weeks. Results: The expression levels of lipopolysaccharide (LPS), inducible nitric oxidase synthase (iNOS), and prostaglandin E2 (PGE2) remarkably increased in AD, but were suppressed by MC administration. As a result, the degradation of filaggrin by PGE2 was suppressed. Furthermore, in AD, iNOS induced macrophage type 1 and increased NO levels. In contrast, due to suppression of iNOS with MC administration, macrophages shifted to type 2 and an increase in L-ornithine was observed, which subsequently promoted filaggrin synthesis. Conclusions: These findings indicate that the AD-like skin symptoms were decelerated by MC via the regulation of the LPS/iNOS/PGE2/filaggrin and LPS/iNOS/Arginase 1/L-ornithine/ filaggrin signaling pathways.