Insulin-like growth factor 1 enhances follicle-stimulating hormone-induced phosphorylation of GATA4 in rat granulosa cells.
Insulin-like growth factor 1 enhances follicle-stimulating hormone-induced phosphorylation of GATA4 in rat granulosa cells.
复制标题
胰岛素样生长因子 1 增强大鼠颗粒细胞中促卵泡激素诱导的 GATA4 磷酸化。
DOI：
10.1016/j.mce.2022.111807
复制
发表时间：
2023
影响因子：
4.1
通讯作者：
Stocco,Carlos
中科院分区：
文献类型：
--
作者：
Convissar,Scott;Bennett-Toomey,Jill;Stocco,Carlos
排卵前颗粒细胞（GC）的分化对于卵母细胞的成熟和从卵巢中释放是必不可少的。我们以前已经证明，卵泡刺激素（FSH）和胰岛素样生长因子（IGFs）密切相互作用，以控制GC功能。同样，我们发现GATA 4介导FSH的作用，并且是排卵前卵泡形成所必需的。本报告旨在确定FSH对GATA 4磷酸化的体内作用，并研究FSH和IGF 1是否相互作用以调节GATA 4活性。在大鼠卵巢中，用马绒毛膜促性腺激素（eCG）处理增加了GATA 4的磷酸化，其仅限于GC的细胞核。使用原代大鼠GC，我们观察到GATA 4在丝氨酸105处的磷酸化增加了该转录因子的转录活性。与FSH一样，IGF 1刺激GATA 4在丝氨酸105处磷酸化。有趣的是，与FSH或IGF 1单独相比，FSH和IGF 1共处理的细胞中GATA 4磷酸化显著更高，表明IGF 1增强了FSH对GATA 4的作用。IGF 1的增强效应需要AKT活性，并且通过抑制糖原合成酶激酶-3 β（GSK 3 β）来模拟，这表明AKT抑制GSK 3 β可能在调节GATA 4磷酸化中起作用。这些数据支持IGF 1/AKT/GSK 3 β信号通路在调节GATA 4转录活性中的重要作用，并为FSH和IGF 1调节GC分化的机制提供了新的见解。我们的研究结果表明，GATA 4转录激活可能，至少部分地，介导AKT行动在GC。
Preovulatory granulosa cell (GC) differentiation is essential for the maturation and release of oocytes from the ovary. We have previously demonstrated that follicle-stimulating hormone (FSH) and insulin-like growth factors (IGFs) closely interact to control GC function. Similarly, we showed that GATA4 mediates FSH actions and it is required for preovulatory follicle formation. This report aimed to determinein vivothe effect of FSH on GATA4 phosphorylation and to investigate whether FSH and IGF1 interact to regulate GATA4 activity. In rat ovaries, treatment with equine chorionic gonadotropin (eCG) increased the phosphorylation of GATA4, which was confined to the nucleus of GCs. Using primary rat GCs, we observed that GATA4 phosphorylation at serine 105 increases the transcriptional activity of this transcription factor. Like FSH, IGF1 stimulated GATA4 phosphorylation at serine 105. Interestingly, GATA4 phosphorylation was significantly higher in cells cotreated with FSH and IGF1 when compared to FSH or IGF1 alone, suggesting that IGF1 augments the effects of FSH on GATA4. It was also found that the enhancing effect of IGF1 requires AKT activity and is mimicked by the inhibition of glycogen synthase kinase-3 β (GSK3β), suggesting that AKT inhibition of GSK3β may play a role in the regulation of GATA4 phosphorylation. The data support an important role of the IGF1/AKT/GSK3β signaling pathway in the regulation of GATA4 transcriptional activity and provide new insights into the mechanisms by which FSH and IGF1 regulate GC differentiation. Our findings suggest that GATA4 transcriptional activation may, at least partially, mediate AKT actions in GCs.