AUTHOR=Wang Wang-Sheng , Guo Chun-Ming , Sun Kang TITLE=Cortisol Regeneration in the Fetal Membranes, A Coincidental or Requisite Event in Human Parturition? JOURNAL=Frontiers in Physiology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2020.00462 DOI=10.3389/fphys.2020.00462 ISSN=1664-042X ABSTRACT=

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.