Department of Health Sciences, Illinois State University, Normal, IL, USA.
J Steroid Biochem Mol Biol. 2014 Jan;139:173-81. doi: 10.1016/j.jsbmb.2013.01.015. Epub 2013 Feb 11.
Preterm birth is a major cause of neonatal morbidity and mortality. Progesterone plays a critical role in suppressing the inflammatory signals that would induce parturition prior to term. Progesterone signaling is regulated in a variety of ways during pregnancy. Endocrine production of high levels of progesterone by the placenta ensures the availability of high levels of progesterone throughout pregnancy. Paracrine regulation of progesterone metabolism in target tissues, particularly the myometrium and cervix, also determines the amount of progesterone ligand available. Progesterone metabolism can also lead to the formation of metabolites that contribute to its effects. In particular, 5β-dihydroprogesterone formation by aldo-keto reductase 1D1 appears to play an important role in maintaining uterine quiescence. Progesterone signaling can also be regulated at the receptor level through changes in the relative expression of the nuclear progesterone receptor isoforms, reduced expression of membrane receptors, and changes in the expression levels of coactivators and/or corepressors, including nuclear factor κB. Progesterone and 17α-hydroxyprogesterone caproate (17OH-PC) have recently been shown to reduce preterm births in women with previous preterm birth or shortened cervix. It is important to realize that these two progestins are likely to act in significantly different ways, which will likely influence their efficacy. The structural differences and resistance to metabolism exhibited by 17OH-PC means that it will be unable to activate some of the pathways that progesterone activates, but that it also will not be subject to paracrine inactivation. The fact that progesterone therapy works for maintaining pregnancy in some women, indicates that for those women insufficient levels of progesterone ligand in target tissues is a determining factor in early parturition, despite high levels of circulating progesterone. This article is part of a Special Issue entitled 'Pregnancy and Steroids'.
早产是新生儿发病率和死亡率的主要原因。孕酮在抑制分娩前的炎症信号方面起着关键作用。孕酮信号在怀孕期间以多种方式进行调节。胎盘产生高水平的孕激素是内分泌产生的，以确保整个怀孕期间孕激素的可用性。旁分泌调节孕酮在靶组织中的代谢，特别是在子宫肌层和子宫颈，也决定了可用的孕酮配体的数量。孕酮代谢也会导致形成有助于其作用的代谢物。特别是，醛酮还原酶 1D1 形成的 5β-二氢孕酮似乎在维持子宫静止方面起着重要作用。孕酮信号也可以通过核孕酮受体亚型的相对表达的变化、膜受体表达减少以及共激活剂和/或核心抑制剂（包括核因子κB）表达水平的变化在受体水平上进行调节。最近已经表明，孕酮和 17α-羟孕酮己酸酯（17OH-PC）可减少有早产史或宫颈缩短的妇女的早产。重要的是要认识到，这两种孕激素可能以非常不同的方式发挥作用，这可能会影响它们的疗效。17OH-PC 表现出的结构差异和对代谢的抗性意味着它将无法激活孕酮激活的一些途径，但它也不会受到旁分泌失活的影响。孕酮治疗对维持某些妇女妊娠有效，这表明对于那些靶组织中孕激素配体水平不足的妇女，尽管循环孕酮水平高，但孕激素配体水平不足是早期分娩的决定因素。本文是特刊“妊娠与甾体”的一部分。
