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Article

Sex Differences in Photoprotective Responses to 1,25-Dihydroxyvitamin D3 in Mice Are Modulated by the Estrogen Receptor-β

1
Department of Physiology, University of Sydney, Sydney, NSW 2006, Australia
2
Anatomy and Histology, University of Sydney, Sydney, NSW 2006, Australia
3
Dermatology, Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2006, Australia
4
Faculty of Veterinary Science, University of Sydney, Sydney, NSW 2006, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: Andrzej Slominski
Int. J. Mol. Sci. 2021, 22(4), 1962; https://doi.org/10.3390/ijms22041962
Received: 15 December 2020 / Revised: 9 February 2021 / Accepted: 9 February 2021 / Published: 16 February 2021
Susceptibility to photoimmune suppression and photocarcinogenesis is greater in male than in female humans and mice and is exacerbated in female estrogen receptor-beta knockout (ER-β−/−) mice. We previously reported that the active vitamin D hormone, 1,25-dihydroxyvitamin D3 (1,25(OH)2D), applied topically protects against the ultraviolet radiation (UV) induction of cutaneous cyclobutane pyrimidine dimers (CPDs) and the suppression of contact hypersensitivity (CHS) in female mice. Here, we compare these responses in female versus male Skh:hr1 mice, in ER-β−/−/−− versus wild-type C57BL/6 mice, and in female ER-blockaded Skh:hr1 mice. The induction of CPDs was significantly greater in male than female Skh:hr1 mice and was more effectively reduced by 1,25(OH)2D in female Skh:hr1 and C57BL/6 mice than in male Skh:hr1 or ER-β−/− mice, respectively. This correlated with the reduced sunburn inflammation due to 1,25(OH)2D in female but not male Skh:hr1 mice. Furthermore, although 1,25(OH)2D alone dose-dependently suppressed basal CHS responses in male Skh:hr1 and ER-β−/− mice, UV-induced immunosuppression was universally observed. In female Skh:hr1 and C57BL/6 mice, the immunosuppression was decreased by 1,25(OH)2D dose-dependently, but not in male Skh:hr1, ER-β−/−, or ER-blockaded mice. These results reveal a sex bias in genetic, inflammatory, and immune photoprotection by 1,25(OH)2D favoring female mice that is dependent on the presence of ER-β. View Full-Text
Keywords: 1α,25-dihydroxyvitaminD3; photoprotection; DNA damage; cyclobutane pyrimidine dimers; edema; photoimmune suppression; female vs. male mice; ER-β knockout 1α,25-dihydroxyvitaminD3; photoprotection; DNA damage; cyclobutane pyrimidine dimers; edema; photoimmune suppression; female vs. male mice; ER-β knockout
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MDPI and ACS Style

Tongkao-on, W.; Yang, C.; McCarthy, B.Y.; De Silva, W.G.M.; Rybchyn, M.S.; Gordon-Thomson, C.; Dixon, K.M.; Halliday, G.M.; Reeve, V.E.; Mason, R.S. Sex Differences in Photoprotective Responses to 1,25-Dihydroxyvitamin D3 in Mice Are Modulated by the Estrogen Receptor-β. Int. J. Mol. Sci. 2021, 22, 1962. https://doi.org/10.3390/ijms22041962

AMA Style

Tongkao-on W, Yang C, McCarthy BY, De Silva WGM, Rybchyn MS, Gordon-Thomson C, Dixon KM, Halliday GM, Reeve VE, Mason RS. Sex Differences in Photoprotective Responses to 1,25-Dihydroxyvitamin D3 in Mice Are Modulated by the Estrogen Receptor-β. International Journal of Molecular Sciences. 2021; 22(4):1962. https://doi.org/10.3390/ijms22041962

Chicago/Turabian Style

Tongkao-on, Wannit, Chen Yang, Bianca Y. McCarthy, Warusavithana G.M. De Silva, Mark S. Rybchyn, Clare Gordon-Thomson, Katie M. Dixon, Gary M. Halliday, Vivienne E. Reeve, and Rebecca S. Mason. 2021. "Sex Differences in Photoprotective Responses to 1,25-Dihydroxyvitamin D3 in Mice Are Modulated by the Estrogen Receptor-β" International Journal of Molecular Sciences 22, no. 4: 1962. https://doi.org/10.3390/ijms22041962

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