Cortisol Regeneration in the Fetal Membranes, A Coincidental or Requisite Event in Human Parturition?
Cortisol Regeneration in the Fetal Membranes, A Coincidental or Requisite Event in Human Parturition?
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DOI：
10.3389/fphys.2020.00462
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发表时间：
2020-05
影响因子：
4
通讯作者：
Wangsheng Wang;Chunming Guo;Kang Sun
中科院分区：
文献类型：
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作者：
Wangsheng Wang;Chunming Guo;Kang Sun
通过 11β-羟基类固醇脱氢酶 1 (11β-HSD1) 的还原酶活性，胎膜具有高皮质醇再生能力。胎膜中 11β-HSD1 的表达受到皮质醇的前馈诱导，而促炎细胞因子会增强皮质醇的前馈诱导。因此，11β-HSD1 的丰度随着胎龄的增加而增加，而且在分娩时，胎膜中皮质醇浓度也会增加。累积的皮质醇参与胎膜中与分娩开始相关的许多关键事件，包括细胞外基质 (ECM) 重塑和刺激前列腺素输出。皮质醇通过多种方法重塑 ECM，包括诱导胶原蛋白 I、III 和 IV 降解以及抑制其交联。皮质醇的这些作用是通过激活自噬、蛋白酶体和基质金属蛋白酶 7 途径以及抑制膜间充质细胞中交联酶赖氨酰氧化酶的表达来实现的。在前列腺素输出方面，皮质醇不仅通过诱导羊膜中的胞质磷脂酶 A2、环氧合酶 2 和羰基还原酶 1 等合成酶来增加前列腺素 E2 和 F2α 的合成，而且还通过抑制绒毛膜中的代谢酶 15-羟基前列腺素脱氢酶来减少其降解。总而言之，迄今为止积累的数据表明，胎膜中 11β-HSD1 的前馈皮质醇再生是分娩开始时的必要事件，并且皮质醇对前列腺素合成和 ECM 重塑的影响可能会通过绒毛膜羊膜炎中的促炎细胞因子而增强。
The fetal membranes are equipped with high capacity of cortisol regeneration through the reductase activity of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1). The expression of 11β-HSD1 in the fetal membranes is under the feedforward induction by cortisol, which is potentiated by proinflammatory cytokines. As a result, the abundance of 11β-HSD1 increases with gestational age and furthermore at parturition with an escalation of cortisol concentration in the fetal membranes. Accumulated cortisol takes parts in a number of crucial events pertinent to the onset of labor in the fetal membranes, including extracellular matrix (ECM) remodeling and stimulation of prostaglandin output. Cortisol remodels the ECM through multiple approaches including induction of collagen I, III, and IV degradation, as well as inhibition of their cross-linking. These effects of cortisol are executed through activation of the autophagy, proteasome, and matrix metalloprotease 7 pathways, as well as inhibition of the expression of cross-linking enzyme lysyl oxidase in mesenchymal cells of the membranes. With regard to prostaglandin output, cortisol not only increases prostaglandin E2 and F2α syntheses through induction of their synthesizing enzymes such as cytosolic phospholipase A2, cyclooxygenase 2, and carbonyl reductase 1 in the amnion, but also decreases their degradation through inhibition of their metabolizing enzyme 15-hydroxyprostaglandin dehydrogenase in the chorion. Taking all together, data accumulated so far denote that the feedforward cortisol regeneration by 11β-HSD1 in the fetal membranes is a requisite event in the onset of parturition, and the effects of cortisol on prostaglandin synthesis and ECM remodeling may be enhanced by proinflammatory cytokines in chorioamnionitis.