PDF(Pubmed)
Abstract：
Increased cortisol levels in the preovulatory follicular fluid suggests a role of glucocorticoid in human ovulation. However, the mechanisms through which cortisol regulates the ovulatory process remain poorly understood. In this study, we examined the upregulation of f5 mRNA by glucocorticoid and its receptor (Gr) in the preovulatory follicles of zebrafish. Our findings demonstrate a significant increase in 11β-hydroxysteroid dehydrogenase type 2 (hsd11b2), a cortisol response gene, in preovulatory follicles. Additionally, hydrocortisone exerts a dose- and time-dependent upregulation of f5 mRNA in these follicles. Importantly, this stimulatory effect is Gr-dependent, as it was completely abolished in gr-/- mutants. Furthermore, site-directed mutagenesis identified a glucocorticoid response element (GRE) in the promoter of zebrafish f5. Interestingly, successive incubation of hydrocortisone and the native ovulation-inducing steroid, progestin (17α,20β-dihydroxy-4-pregnen-3-one, DHP), further enhanced f5 expression in preovulatory follicles. Overall, our results indicate that the dramatic increase of f5 expression in preovulatory follicles is partially attributable to the regulation of glucocorticoid and Gr.
摘要：
排卵前卵泡液中皮质醇水平升高提示糖皮质激素在人类排卵中的作用。然而,皮质醇调节排卵过程的机制仍然知之甚少。在这项研究中,我们检测了斑马鱼排卵前卵泡中糖皮质激素及其受体（Gr）对f5mRNA的上调。我们的研究结果表明，11β-羟基类固醇脱氢酶2型（hsd11b2）显着增加，皮质醇反应基因，在排卵前卵泡。此外,氢化可的松在这些卵泡中发挥f5mRNA的剂量和时间依赖性上调。重要的是,这种刺激作用是Gr依赖性的,因为它在gr-/-突变体中被完全废除了。此外，定点诱变鉴定了斑马鱼f5启动子中的糖皮质激素反应元件（GRE）。有趣的是,连续孵育氢化可的松和天然诱导排卵的类固醇，孕激素（17α，20β-二羟基-4-孕烯-3-酮，DHP),进一步增强了f5在排卵前卵泡中的表达。总的来说,我们的结果表明，排卵前卵泡中f5表达的急剧增加部分归因于糖皮质激素和Gr的调节。
