Membrane Estrogen Receptor (GPER) and Follicle-Stimulating Hormone Receptor (FSHR) Heteromeric Complexes Promote Human Ovarian Follicle Survival.
Membrane Estrogen Receptor (GPER) and Follicle-Stimulating Hormone Receptor (FSHR) Heteromeric Complexes Promote Human Ovarian Follicle Survival.
复制标题
DOI：
10.1016/j.isci.2020.101812
复制
发表时间：
2020-12-18
期刊：
影响因子：
5.8
通讯作者：
Simoni M
中科院分区：
文献类型：
--
作者：
Casarini L;Lazzaretti C;Paradiso E;Limoncella S;Riccetti L;Sperduti S;Melli B;Marcozzi S;Anzivino C;Sayers NS;Czapinski J;Brigante G;Potì F;La Marca A;De Pascali F;Reiter E;Falbo A;Daolio J;Villani MT;Lispi M;Orlando G;Klinger FG;Fanelli F;Rivero-Müller A;Hanyaloglu AC;Simoni M
经典地，促卵泡激素受体（FSHR）驱动的cAMP介导的信号传导促进人类卵泡生长和卵母细胞成熟。然而，矛盾的体外数据提出了不同的观点FSHR介导的cAMP信号的生理意义。我们发现G蛋白偶联雌激素受体（GPER）与FSHR异聚化，将cAMP/死亡信号重编程为维持卵母细胞存活的基本增殖刺激。在人类颗粒细胞中，在高FSHR：GPER比率下，存活信号缺失，这对卵泡成熟产生负面影响，并与接受控制性卵巢刺激的患者的优先Gαs蛋白/cAMP途径偶联和FSH反应性密切相关。相反，FSHR/GPER异聚体触发通过Gβγ二聚体传递的抗凋亡/增殖FSH信号，而异聚体形成或GPER敲低的损伤增强了FSH依赖性细胞死亡和类固醇生成。因此，我们的研究结果表明，卵母细胞的成熟取决于GPER的能力，形状FSHR选择性信号，表明激素受体异聚体可能是细胞增殖的标志。G蛋白偶联雌激素受体（GPER）与FSH受体（FSHR）相互作用FSHR/GPER异聚体将FSH诱导的死亡信号重新编程为增殖刺激异聚体的抗凋亡信号传导是通过GPER-Gαs抑制复合物和Gβγ异聚体的形成影响IVF患者的卵泡成熟和FSH反应分子生物学;女性生殖内分泌学;内分泌调节
Classically, follicle-stimulating hormone receptor (FSHR)-driven cAMP-mediated signaling boosts human ovarian follicle growth and oocyte maturation. However, contradicting in vitro data suggest a different view on physiological significance of FSHR-mediated cAMP signaling. We found that the G-protein-coupled estrogen receptor (GPER) heteromerizes with FSHR, reprogramming cAMP/death signals into proliferative stimuli fundamental for sustaining oocyte survival. In human granulosa cells, survival signals are missing at high FSHR:GPER ratio, which negatively impacts follicle maturation and strongly correlates with preferential Gαs protein/cAMP-pathway coupling and FSH responsiveness of patients undergoing controlled ovarian stimulation. In contrast, FSHR/GPER heteromers triggered anti-apoptotic/proliferative FSH signaling delivered via the Gβγ dimer, whereas impairment of heteromer formation or GPER knockdown enhanced the FSH-dependent cell death and steroidogenesis. Therefore, our findings indicate how oocyte maturation depends on the capability of GPER to shape FSHR selective signals, indicating hormone receptor heteromers may be a marker of cell proliferation. G-protein-coupled estrogen receptor (GPER) interacts with FSH receptor (FSHR) FSHR/GPER heteromers reprogram FSH-induced death signals to proliferative stimuli Anti-apoptotic signaling of heteromers is via a GPER-Gαs inhibitory complex and Gβγ Heteromer formation impacts follicle maturation and FSH responses of IVF patients Molecular Biology; Female Reproductive Endocrinology; Endocrine Regulation
登录
查看更多内容
影响因子：
3.7
作者：
AHARONI, D;DANTES, A;AMSTERDAM, A
通讯作者：
AMSTERDAM, A
影响因子：
3.7
作者：
Heublein S;Mayr D;Vrekoussis T;Friese K;Hofmann SS;Jeschke U;Lenhard M
通讯作者：
Lenhard M
影响因子：
4
作者：
Breckwoldt, M.;Selvaraj, N.;Amsterdam, A.
通讯作者：
Amsterdam, A.
影响因子：
4.1
作者：
Brigante, Giulia;Riccetti, Laura;Casarini, Livio
通讯作者：
Casarini, Livio
影响因子：
5.8
作者：
Amsterdam, A;Sasson, R;Hirsh, L
通讯作者：
Hirsh, L