Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 15 December 2020 / Approved: 16 December 2020 / Online: 16 December 2020 (08:49:22 CET)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Int. J. Mol. Sci. 2021, 22, 1962
DOI: 10.3390/ijms22041962

Abstract

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 ultraviolet radiation (UV)-induction of cutaneous cyclobutane pyrimidine dimers (CPDs) and 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. 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 reduced sunburn inflammation by 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.

Keywords

1α,25-dihydroxyvitaminD3; photoprotection; DNA damage; cyclobutane pyrimidine dimers; edema; photoimmune suppression; female vs male mice; ER-β knockout

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