Ben-Zimra Micha, Koler Moriah, Melamed-Book Naomi, Arensburg Jonathan, Payne Anita H, Orly Joseph
Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
Mol Cell Endocrinol. 2002 Feb 22;187(1-2):223-31. doi: 10.1016/s0303-7207(01)00713-4.
The ontogeny and functional role of steroidogenesis during mammalian gestation is poorly understood. This review provides a summary of our recent findings on the spatio-temporal expression of key steroidogenic genes controlling progesterone synthesis in the uterus during mouse pregnancy. We have shown that onset of cholesterol side chain cleavage cytochrome P450 (P450scc) and a newly identified isoform of murine 3beta-hydroxysteroid dehydrogenase/isomerase type VI (3betaHSD VI) expression occurs upon decidualization of the uterine wall induced by implantation. This unexpected early expression of the enzymes in the maternal decidua is terminated at mid-pregnancy when the steroidogenic ability reappears in the extraembryonic giant cells at the time of placentation. The giant cells express another protein indispensable for steroid hormone synthesis in the adrenal and gonads, Steroidogenic Acute Regulatory (StAR) protein. Unlike the human placenta, the steroidogenic genes are not expressed in the cells of the mature mouse placenta during the second half of gestation. Finally, our studies suggest that transcriptional regulation of P450scc is mediated by a non-SF-1 protein that substitutes SF-1 functions in the extraembryonic cells. Collectively, the results of the present study suggest that, during early phases of pregnancy, local progesterone synthesis in the maternal decidua and the trophoblast layers surrounding the embryonal cavity is important for successful implantation and/or maintenance of pregnancy. We propose that the local production of progesterone acts as an immunosuppressant at the maternofetal interface preventing the rejection of the fetal allograft.
哺乳动物妊娠期类固醇生成的个体发生及其功能作用尚不清楚。本综述总结了我们最近关于小鼠妊娠期间子宫中控制孕酮合成的关键类固醇生成基因时空表达的研究结果。我们发现，胆固醇侧链裂解细胞色素P450（P450scc）和新鉴定的小鼠VI型3β-羟基类固醇脱氢酶/异构酶（3βHSD VI）同工型的表达在植入诱导的子宫壁蜕膜化时开始。母体蜕膜中这些酶的这种意外早期表达在妊娠中期终止，此时类固醇生成能力在胎盘形成时出现在胚外巨细胞中。巨细胞表达肾上腺和性腺中类固醇激素合成所必需的另一种蛋白质，类固醇生成急性调节（StAR）蛋白。与人类胎盘不同，妊娠后期成熟小鼠胎盘的细胞中不表达类固醇生成基因。最后，我们的研究表明，P450scc的转录调控由一种非SF-1蛋白介导，该蛋白在胚外细胞中替代SF-1的功能。总的来说，本研究结果表明，在妊娠早期，母体蜕膜和围绕胚腔的滋养层中的局部孕酮合成对于成功植入和/或维持妊娠很重要。我们提出，局部产生的孕酮在母胎界面处作为一种免疫抑制剂，防止胎儿同种异体移植被排斥。
