While flavonoids have been studied extensively for estrogen receptor activity, they have not been well studied for their ability to modify progesterone receptor (PR) and glucocorticoid receptor (GR) signaling. Three flavonoid compounds, tangeretin, wogonin, and baicalein, were selected for testing for PR and GR activity based on their structural similarity to known phytoprogesterone-like compounds. Each compound was docked in the binding pocket of PR and GR. Of these compounds, baicalein was predicted to be most likely to bind to both receptors. A fluorescence polarization competitive binding assay for PR and GR confirmed that baicalein binds to both the PR and GR with IC₅₀ values of 15.30 μM and 19.26 μM, respectively. In Ishikawa PR-B and T47D cells, baicalein acted as a PR antagonist in a hormone response element (HRE) luciferase (Luc) assay. In OVCAR5 cells, which only express GR, baicalein was a GR agonist via an HRE/Luc assay and induced GR target genes, FKBP5 and GILZ. RU486, a PR and GR antagonist, abrogated baicalein’s activity in OVCAR5 cells, confirming baicalein’s activity is mediated through the GR. In vivo, baicalein administered intraperitoneally to female mice twice a week for 4 weeks at a dose of 25 mg/kg induced the GR target gene GILZ in the reproductive tract, which was blocked by RU486. In summary, baicalein has PR antagonist and GR agonist activity in vitro and demonstrates GR agonist activity in the uterus in vivo.

中文翻译：

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黄ical素是一种通过孕酮和糖皮质激素受体发出信号的植物激素。

尽管已对类黄酮的雌激素受体活性进行了广泛研究，但尚未就其修饰黄体酮受体（PR）和糖皮质激素受体（GR）信号传导的能力进行深入研究。基于三种类黄酮化合物，即橘皮苷，wogonin和黄ical素，根据其与已知植物雌激素样化合物的结构相似性，选择用于PR和GR活性测试。每种化合物都对接在PR和GR的结合口袋中。在这些化合物中，黄ical素预计最有可能与两种受体结合。PR和GR的荧光偏振竞争结合测定法证实黄ical素以IC ₅₀结合PR和GR分别为15.30μM和19.26μM。在石川PR-B和T47D细胞中，黄ical素在激素反应元件（HRE）荧光素酶（Luc）分析中充当PR拮抗剂。在仅表达GR的OVCAR5细胞中，黄ical素通过HRE / Luc分析并诱导GR目标基因FKBP5和GILZ成为GR激动剂。PR和GR拮抗剂RU486消除了黄ical素在OVCAR5细胞中的活性，证实黄ical素的活性是通过GR介导的。在体内，以25 mg / kg的剂量每周两次向雌性小鼠腹膜内施用黄ical素4周，诱导了生殖道中的GR靶基因GILZ，该基因被RU486阻断。总之，黄ical素在体外具有PR拮抗剂和GR激动剂活性，并且在体内子宫中表现出GR激动剂活性。