Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA.
J Clin Endocrinol Metab. 2010 May;95(5):2271-5. doi: 10.1210/jc.2009-2136. Epub 2010 Mar 17.
Unchanging plasma progesterone (P4) levels suggest that human labor is initiated by reduced P4 receptor (PR) expression, which elicits functional P4 withdrawal. The glucocorticoid receptor (GR) is also implicated in this process.
Our objective was to compare PR and GR staining in human decidual cells (DCs) and interstitial trophoblasts (ITs) of gestational age-matched pre- and postcontraction specimens and to evaluate steroid effects on PR and GR expression in human DC cultures.
Decidua basalis and parietalis sections were immunostained for PR or GR and then for the cytoplasmic DC and IT markers vimentin and cytokeratin. Western blotting measured PR and GR levels in nuclear extracts of cultured leukocyte-free term DCs after incubation with estradiol-17beta (E2) with or without medroxyprogesterone acetate (MPA).
PR histological scores (HSCOREs) were significantly higher in DC nuclei from pre- vs. post-uterine-contraction decidua basalis and parietalis sections with PR immunostaining absent from ITs. In contrast, immunoreactive GR was localized in IT and DC nuclei. GR HSCORES were significantly higher in ITs than DCs but similar in pre- vs. post-uterine-contraction specimens. In term DC monolayers, PR-A and PR-B were enhanced by E2 and inhibited by MPA, whereas E2 plus MPA produced intermediate PR expression. The GR was constitutively expressed.
In post- vs. pre-uterine-contraction specimens, significantly lower HSCOREs in DC nuclei, but not IT, and unchanging GR levels in DCs and ITs suggest that functional P4 withdrawal may occur in DCs and is unlikely to involve the GR. Nuclear extracts from DC monolayer cultures express steroid-regulated PR-A and PR-B and constitutive GR.
不变的血浆孕酮（P4）水平表明，人类分娩是由 P4 受体（PR）表达减少引起的，这引发了功能性 P4 撤退。糖皮质激素受体（GR）也与此过程有关。
我们的目的是比较妊娠年龄匹配的分娩前和分娩后子宫收缩标本中人类蜕膜细胞（DC）和间质滋养层（IT）中 PR 和 GR 的染色，并评估类固醇对人 DC 培养物中 PR 和 GR 表达的影响。
对蜕膜基底和壁部切片进行 PR 或 GR 免疫染色，然后用细胞质 DC 和 IT 标志物波形蛋白和细胞角蛋白进行染色。用白细胞游离足月 DC 培养物的核提取物进行 Western 印迹，孵育雌二醇-17β（E2）和/或醋酸甲羟孕酮（MPA）后测量 PR 和 GR 水平。
与 IT 缺乏 PR 免疫染色的分娩前和分娩后子宫收缩蜕膜基底和壁部切片相比，DC 核中的 PR 组织学评分（HSCORE）在 DC 核中显著更高。相比之下，免疫反应性 GR 定位于 IT 和 DC 核中。IT 中的 GR HSCORE 明显高于 DC，但分娩前和分娩后标本相似。在足月 DC 单层培养物中，E2 增强 PR-A 和 PR-B，MPA 抑制 PR-A 和 PR-B，而 E2 加 MPA 产生中间 PR 表达。GR 是组成型表达的。
与分娩前标本相比，分娩后标本中 DC 核中的 HSCORE 显著降低，但 IT 中的 HSCORE 没有降低，并且 DC 和 IT 中的 GR 水平保持不变，这表明功能性 P4 撤退可能发生在 DC 中，不太可能涉及 GR。DC 单层培养物的核提取物表达受类固醇调节的 PR-A 和 PR-B 和组成型 GR。
