Mitogen-Activated Protein Kinase 8 (MAP3K8) Mediates the Signaling Pathway of Estradiol Stimulating Progesterone Production Through G Protein-Coupled Receptor 30 (GPR30) in Mouse Corpus Luteum
Mitogen-Activated Protein Kinase 8 (MAP3K8) Mediates the Signaling Pathway of Estradiol Stimulating Progesterone Production Through G Protein-Coupled Receptor 30 (GPR30) in Mouse Corpus Luteum
复制标题
丝裂原激活蛋白激酶 8 (MAP3K8) 通过 G 蛋白偶联受体 30 (GPR30) 介导小鼠黄体中雌二醇刺激孕酮产生的信号通路
DOI：
10.1210/me.2015-1009
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发表时间：
2015-05-01
影响因子：
--
通讯作者：
Cui, Sheng
中科院分区：
文献类型：
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作者：
Liu, Ying;Li, Yueqin;Cui, Sheng
黄体（corpus luteum，CL）是由排卵卵泡发育而来的短暂内分泌腺体，其最重要的功能是合成和分泌孕酮（P-4），孕酮是维持哺乳动物正常妊娠和发情周期的关键激素。雌激素在促进CL中P-4的合成中具有重要作用，但雌二醇（E2）调节CL中P-4合成的机制尚不清楚。本研究结果首次表明，所有CL细胞均表达MAPK 8（MAP 3 K8），且在CL发生的中期，MAP 3 K8的表达水平明显高于早期和晚期。进一步的功能研究表明，通过使用MAP 3 K8小干扰RNA和MAP 3 K8信号传导抑制剂（MAP 3 K8 i）强制抑制黄体细胞中的内源性MAP 3 K8，可显著阻断CL中P-4的合成，并中和E-2对P-4产生的促进作用。此外，我们的研究结果表明，E-2对P-4合成的刺激作用依赖于雌激素非经典蛋白偶联受体30，而MAP 3 K8通过刺激ERK磷酸化参与介导E-2的蛋白偶联受体30信号通路影响P-4合成。这些新的发现对于我们理解卵巢的生理和病理机制是至关重要的。
The corpus luteum (CL) is a transient endocrine gland developed from the ovulated follicles, and the most important function is to synthesize and secrete progesterone (P-4), a key hormone to maintain normal pregnancy and estrous cycle in most mammals. It is known that estrogen has a vital role in stimulating P-4 synthesis in CL, but it still remains unclear about the mechanism of estradiol (E-2) regulating P-4 production in CL. Our results here first show that all of the CL cells express MAPK 8 (MAP3K8), and the MAP3K8 level is much higher at the midstage than at the early and late stages during CL development. The further functional studies show that the forced inhibition of endogenous MAP3K8 by using MAP3K8 small interfering RNA and MAP3K8 signaling inhibitor (MAP3K8i) in the luteal cells significantly block the P-4 synthesis and neutralize the enhancing effect of E-2 on P-4 production in the CL. In addition, our results here demonstrate that the stimulating effect of E-2 on P-4 synthesis relies on the estrogen no-classical protein-coupled receptor 30, and MAP3K8 is involved in mediating the protein-coupled receptor 30signaling of E-2 affecting P-4 synthesis via stimulating ERK phosphorylation. These novel findings are critical for our understanding the ovary physiology and pathological mechanism.