Maternal glucocorticoids critically rise during pregnancy reaching up to a 20-fold increase of mid-pregnancy concentrations. Concurrently, another steroid hormone, progesterone, increases. Progesterone, which shows structural similarities to glucocorticoids, can bind the intracellular glucocorticoid receptor, although with lower affinity. Progesterone is essential for the establishment and continuation of pregnancy and it is generally acknowledged to promote maternal immune tolerance to fetal alloantigens through a wealth of immunomodulatory mechanisms. Despite the potent immunomodulatory capacity of glucocorticoids, little is known about their role during pregnancy. Here we aim to compare general aspects of glucocorticoids and progesterone during pregnancy, including shared common steroidogenic pathways, plasma transporters, regulatory pathways, expression of receptors, and mechanisms of action in immune cells. It was recently acknowledged that progesterone receptors are not ubiquitously expressed on immune cells and that pivotal features of progesterone induced- maternal immune adaptations to pregnancy are mediated via the glucocorticoid receptor, including e.g., T regulatory cells expansion. We hypothesize that a tight equilibrium between progesterone and glucocorticoids is critically required and recapitulate evidence supporting that their disequilibrium underlie pregnancy complications. Such a disequilibrium can occur, e.g., after maternal stress perception, which triggers the release of glucocorticoids and impair progesterone secretion, resulting in intrauterine inflammation. These endocrine misbalance might be interconnected, as increase in glucocorticoid synthesis, e.g., upon stress, may occur in detriment of progesterone steroidogenesis, by depleting the common precursor pregnenolone. Abundant literature supports that progesterone deficiency underlies pregnancy complications in which immune tolerance is challenged. In these settings, it is largely yet undefined if and how glucocorticoids are affected. However, although progesterone immunomodulation during pregnancy appear to be chiefly mediated glucocorticoid receptors, excess glucocorticoids cannot compensate by progesterone deficiency, indicating that additional und still undercover mechanisms are at play.

中文翻译：

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类固醇，妊娠和胎儿发育。

孕妇的糖皮质激素在妊娠期间会严重升高，达到中期妊娠浓度的20倍。同时，另一类固醇激素，孕酮增加。孕酮与糖皮质激素的结构相似，尽管亲和力较低，但它可以结合细胞内糖皮质激素受体。孕酮对于妊娠的建立和延续至关重要，并且公认通过多种免疫调节机制促进孕产妇对胎儿同种异体抗原的免疫耐受。尽管糖皮质激素具有强大的免疫调节能力，但对其在妊娠期间的作用知之甚少。在这里，我们旨在比较妊娠期间糖皮质激素和孕激素的一般方面，包括共有的常见类固醇生成途径，血浆转运蛋白，调节途径，受体的表达以及免疫细胞中的作用机制。最近已经认识到，孕激素受体并未在免疫细胞上普遍表达，孕激素诱导的母体对妊娠的免疫适应性的关键特征是通过糖皮质激素受体介导的，包括例如T调节细胞的扩张。我们假设迫切需要孕酮和糖皮质激素之间的严格平衡，并概括证明其不平衡是妊娠并发症的基础的证据。这种不平衡可能发生在例如母体压力感知之后，这触发了糖皮质激素的释放并损害孕激素的分泌，导致子宫内炎症。这些内分泌失衡可能是相互关联的，因为糖皮质激素合成的增加，例如 在压力下，通过消耗常见的前体孕烯醇酮，可能会损害孕激素类固醇生成。大量文献支持孕酮缺乏是孕育并发症的基础，在孕育并发症中，免疫耐受受到了挑战。在这些情况下，糖皮质激素是否以及如何受到影响尚不确定。然而，尽管孕期的孕激素免疫调节似乎主要是介导的糖皮质激素受体，但过量的糖皮质激素不能通过孕激素缺乏来补偿，这表明还有其他的秘密机制正在发挥作用。目前尚不清楚糖皮质激素是否以及如何受到影响。然而，尽管孕期的孕激素免疫调节似乎主要是介导的糖皮质激素受体，但过量的糖皮质激素不能通过孕激素缺乏来补偿，这表明还有其他的秘密机制正在发挥作用。目前尚不清楚糖皮质激素是否以及如何受到影响。然而，尽管孕期的孕激素免疫调节似乎主要是介导的糖皮质激素受体，但过量的糖皮质激素不能通过孕激素缺乏来补偿，这表明还有其他的秘密机制正在发挥作用。