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Altered vitamin D 3 metabolism in the ovary and periovarian adipose tissue of rats with letrozole-induced PCOS
Histochemistry and Cell Biology ( IF 2.1 ) Pub Date : 2020-10-23 , DOI: 10.1007/s00418-020-01928-z
Malgorzata Grzesiak 1 , Gabriela Burzawa 2 , Patrycja Kurowska 3 , Klaudia Blaszczyk 3 , Agata Szlaga 4 , Anna Blasiak 4 , Andrzej Sechman 2 , Agnieszka Rak 3
Affiliation  

Vitamin D3 (VD3) 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 VD3 metabolism in the ovary during PCOS. Herein, we investigated differences in the expression of VD3 receptor (VDR) and key VD3 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, VD3 metabolite concentrations in plasma (25OHD) and tissues (ovary and POAT; 1,25(OH)2D3), 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)2D3 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 VD3 metabolism in the ovary and POAT of PCOS rats. The reduced 1,25(OH)2D3 concentration in those tissues suggests their contribution to VD3 deficiency observed in PCOS and might implicate in PCOS pathogenesis.



中文翻译:

来曲唑诱导的PCOS大鼠卵巢和卵巢周围脂肪组织中维生素D 3代谢的改变

维生素D 3(VD 3)在卵巢中起重要作用,其缺乏与卵巢病变有关,包括多囊卵巢综合征(PCOS)。但是,在PCOS期间,卵巢中没有与VD 3代谢相关的数据。在本文中,我们研究了对照(前体)的卵巢和卵巢周围脂肪组织(POAT)中VD 3受体(VDR)和关键VD 3代谢酶1α-羟化酶(CYP27B1)和24-羟化酶(CYP24A1)的表达差异和二烯菊酯)和来曲唑大鼠诱导的PCOS。VdrCyp27b1Cyp24a1测定mRNA表达,检查其蛋白丰度并进行免疫定位。此外,测定血浆(25OHD)和组织(卵巢和POAT; 1,25(OH)2 D 3)中的VD 3代谢物浓度和血浆钙水平。与对照组相比,来曲唑治疗的大鼠中25OHD浓度显着降低,而各组之间的钙浓度没有变化。PCOS大鼠卵巢和POAT中1,25(OH)2 D 3的含量均降低。在卵巢中,我们发现减少CYP27B1和增加VDR来曲唑治疗组和雌二醇对照组的mRNA表达。相应的蛋白质丰度分别下调和上调,但仅在来曲唑处理之后。在POAT中,在来曲唑治疗的大鼠中仅Cyp27b1转录水平和CYP27B1蛋白丰度降低。VDR在健康和囊性卵泡中免疫定位,而CYP27B1和CYP24A1仅在健康卵泡中发现。最后,我们的结果提供了PCOS大鼠卵巢和POAT中VD 3代谢破坏的第一个证据。这些组织中1,25(OH)2 D 3浓度的降低表明它们对PCOS中观察到的VD 3缺乏有贡献,并可能暗示了PCOS的发病机理。

更新日期:2020-10-26
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