The classical progesterone receptor mediates Xenopus oocyte maturation through a nongenomic mechanism

The classical progesterone receptor mediates Xenopus oocyte maturation through a nongenomic mechanism
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DOI:
10.1073/pnas.220302597
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发表时间:
2000-11-07
影响因子:
11.1
通讯作者:
Liu, XJ
Liu, XJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Bayaa, M;Booth, RA;Liu, XJ

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非洲爪哇的卵母细胞在第一次减数分裂的G(2)时发生生理性停滞。恢复减数分裂或卵母细胞成熟是由黄体酮触发的。黄体酮诱导非洲爪哇卵母细胞成熟是通过核外受体介导的,不依赖于基因转录。然而,核外卵母细胞孕激素受体(PR)的识别仍然是一个长期存在的问题。我们已经从非洲爪哇卵母细胞的cDNA文库中分离出了人PR的两栖同源物。克隆的非洲爪哇孕酮受体(XPR)在异种细胞中作为孕酮调节的转录激活子发挥作用。然而,内源性xPR被排除在卵母细胞核之外,而似乎是一种与任何膜结构无关的胞浆蛋白。在非洲爪哇卵母细胞中注射xPR基因可加速孕酮诱导的卵母细胞成熟,并降低所需的孕酮浓度。在去核卵母细胞中,xPR加速了孕酮诱导的丝裂原活化蛋白激酶的激活。这些数据表明,xPR是非洲爪哇卵母细胞受体的长期追求者,与孕酮诱导的卵母细胞成熟有关。
Xenopus laevis oocytes are physiologically arrested at G(2) of meiosis I. Resumption of meiosis, or oocyte maturation, is triggered by progesterone. Progesterone-induced Xenopus oocyte maturation is mediated via an extranuclear receptor and is independent of gene transcription. The identity of this extranuclear oocyte progesterone receptor (PR), however, has remained a longstanding problem. We have isolated the amphibian homologue of human PR from a Xenopus oocyte cDNA library. The cloned Xenopus progesterone receptor (xPR) functioned in heterologous cells as a progesterone-regulated transcription activator. However, endogenous xPR was excluded from the oocyte nucleus and instead appeared to be a cytosolic protein not associated with any membrane structures. Injection of xPR mRNA into Xenopus oocytes accelerated the progesterone-induced oocyte maturation and reduced the required concentrations of progesterone. In enucleated oocytes, xPR accelerated the progesterone-induced mitogen-activated protein kinase activation. These data suggest that xPR is the long sought after Xenopus oocyte receptor responsible for progesterone-induced oocyte maturation.