Department of Molecular Endocrinology, Institute of Experimental Endocrinology, Biomedical Research Center SAS, Bratislava, Slovakia.
Department of Molecular Endocrinology, Institute of Experimental Endocrinology, Biomedical Research Center SAS, Bratislava, Slovakia.
Environ Toxicol Pharmacol. 2018 Apr;59:66-73. doi: 10.1016/j.etap.2018.03.001. Epub 2018 Mar 2.
In the present study, we aimed to examine effects of different concentrations of the endocrine disruptor Bisphenol A (BPA; 1 nM, 1 μM, 100 μM) and the flavonoid fisetin (1, 10, 25, 50 μM), individually and in combinations, on steroidogenic function of porcine ovarian granulosa cells (GCs) represented by progesterone production. We confirmed that BPA inhibited progesterone production by GCs at the highest concentration. Fisetin reduced gonadotropin-stimulated progesterone synthesis dose-dependently, and in this manner, fisetin impaired progesterone production when added to BPA-treated GCs. The mechanisms of the inhibitory effects of the combinations included a significant down-regulation of the key steroidogenesis-related genes (STAR, CYP11A1, HSD3B). Our findings suggest for the first time that fisetin might interfere with ovarian steroidogenesis, and might not have beneficial but rather aggravating effects in terms of modulating progesterone synthesis altered by high concentrations of BPA.
在本研究中，我们旨在研究不同浓度的内分泌干扰物双酚 A（BPA；1nM、1μM、100μM）和类黄酮非瑟酮（1、10、25、50μM）单独和联合作用对猪卵巢颗粒细胞（GC）甾体生成功能的影响，以孕激素产生为代表。我们证实，BPA 在最高浓度下抑制 GC 产生孕激素。非瑟酮剂量依赖性地降低促性腺激素刺激的孕激素合成，并且以这种方式，当添加到 BPA 处理的 GC 中时，非瑟酮会损害孕激素的产生。组合的抑制作用的机制包括关键甾体生成相关基因（STAR、CYP11A1、HSD3B）的显著下调。我们的研究结果首次表明，非瑟酮可能干扰卵巢甾体生成，并且在调节由高浓度 BPA 改变的孕激素合成方面可能没有有益作用，而是具有加重作用。
