Altered vitamin D(3) metabolism in the ovary and periovarian adipose tissue of rats with letrozole-induced PCOS

Vitamin D(3) (VD(3)) plays an important role in the ovary and its deficiency is associated with ovarian pathologies, including polycystic ovary syndrome (PCOS). However, there is no data related to VD(3) metabolism in the ovary during PCOS. Herein, we investigated differences in the expression of VD(3) receptor (VDR) and key VD(3) metabolic enzymes, 1α-hydroxylase (CYP27B1) and 24-hydroxylase (CYP24A1), in the ovary and periovarian adipose tissue (POAT) of control (proestrus and diestrus) and PCOS induced by letrozole rats. Vdr, Cyp27b1 and Cyp24a1 mRNA expression was determined, their protein abundance was examined and immunolocalized. Furthermore, VD(3) metabolite concentrations in plasma (25OHD) and tissues (ovary and POAT; 1,25(OH)(2)D(3)), and plasma calcium level were determined. 25OHD concentration decreased markedly in letrozole-treated rats in comparison with controls, whereas calcium concentration did not vary among the examined groups. The amount of 1,25(OH)(2)D(3) decreased in both ovary and POAT of PCOS rats. In the ovary, we found decreased Cyp27b1 and increased Vdr mRNA expression in letrozole-treated and diestrus control group. Corresponding protein abundances were down-regulated and up-regulated, respectively but only following letrozole treatment. In POAT, only Cyp27b1 transcript level and CYP27B1 protein abundance were decreased in letrozole-treated rats. VDR was immunolocalized in healthy and cystic follicles, while CYP27B1 and CYP24A1 were found exclusively in healthy ones. Concluding, our results provide the first evidence of disrupted VD(3) metabolism in the ovary and POAT of PCOS rats. The reduced 1,25(OH)(2)D(3) concentration in those tissues suggests their contribution to VD(3) deficiency observed in PCOS and might implicate in PCOS pathogenesis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00418-020-01928-z) contains supplementary material, which is available to authorized users.