Cooper E S, Greer I A, Brooks A N
Medical Research Council Reproductive Biology Unit, Centre for Reproductive Biology, Edinburgh, United Kingdom.
J Clin Endocrinol Metab. 1996 Dec;81(12):4462-9. doi: 10.1210/jcem.81.12.8954060.
The objective of this study was to demonstrate the ontogeny of POMC gene expression, the distribution of immunoreactive ACTH, and tissue peptide content within the placenta and fetal membranes and to investigate the regulatory effects of PGs and progesterone during the first trimester and of labor at term. Tissues were collected from the following groups: 1) women undergoing first trimester (gestation 5-12 weeks) therapeutic abortion (by suction curettage with and without the synthetic PGE1 analogue, gemeprost administered vaginally 2-4 h before the procedure or with 600 mg mifepristone 48 h before receiving 1 mg gemeprost vaginally); 2) women undergoing second trimester therapeutic abortion (600 mg mifepristone; 1 mg gemeprost); 3) in association with delivery at term by spontaneous labor; 4) induced labor; or 5) elective caesarean section. ACTH was immunolocalized to the placental cytotrophoblasts in the first trimester and to the syncytiotrophoblasts in the second and third trimester. The intensity of the staining increased with advancing gestation. ACTH immunoreactivity also was localized in the epithelial layer of the amnion, the reticular layer of the chorion, and the decidual stroma. ACTH content measured by RIA in placental extracts increased significantly in the third trimester. In situ hybridization demonstrated expression of POMC messenger RNA in syncytiotrophoblasts and cytotrophoblasts from the first trimester and also demonstrated a significant increase in POMC gene expression with advancing gestation. The localization and staining intensity for ACTH and POMC gene expression were not affected by the administration of PGs or mifepristone or by labor at term. These data demonstrate the localization of ACTH immunoreactivity within the placenta throughout pregnancy, supporting the hypothesis that the placenta may activate and maintain the maternal and/or fetal hypothalamo-pituitary-adrenal axis throughout pregnancy.
本研究的目的是证明促肾上腺皮质激素原（POMC）基因表达的个体发生、免疫反应性促肾上腺皮质激素（ACTH）的分布以及胎盘和胎膜内的组织肽含量，并研究孕早期前列腺素（PGs）和孕酮以及足月分娩时的调节作用。从以下几组收集组织：1）接受孕早期（妊娠5 - 12周）治疗性流产的妇女（通过吸刮术，术前2 - 4小时阴道给予或不给予合成PGE1类似物吉美前列素，或术前48小时给予600mg米非司酮，然后阴道给予1mg吉美前列素）；2）接受孕中期治疗性流产的妇女（600mg米非司酮；1mg吉美前列素）；3）足月自然分娩的产妇；4）引产的产妇；或5）择期剖宫产的产妇。ACTH在孕早期定位于胎盘细胞滋养层，在孕中期和晚期定位于合体滋养层。染色强度随孕周增加而增强。ACTH免疫反应性也定位于羊膜上皮层、绒毛膜网状层和蜕膜基质。放射免疫分析法（RIA）测定胎盘提取物中的ACTH含量在孕晚期显著增加。原位杂交显示孕早期合体滋养层和细胞滋养层中有POMC信使核糖核酸（mRNA）表达，且随着孕周增加POMC基因表达显著增加。ACTH的定位和染色强度以及POMC基因表达不受PGs或米非司酮的给药或足月分娩的影响。这些数据证明了整个孕期ACTH免疫反应性在胎盘内的定位，支持了胎盘可能在整个孕期激活和维持母体和/或胎儿下丘脑 - 垂体 - 肾上腺轴的假说。
