Blockade of estrogen receptors decreases CNS and pituitary prostaglandin synthase expression in fetal sheep
Blockade of estrogen receptors decreases CNS and pituitary prostaglandin synthase expression in fetal sheep
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DOI：
10.1159/000109664
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发表时间：
2008-01-01
影响因子：
4.1
通讯作者：
Wood, Charles E.
中科院分区：
文献类型：
--
作者：
Schaub, Christine E.;Keller-Wood, Maureen;Wood, Charles E.
背景/目的：前列腺素e2 （PGE(2)）和雌二醇均可刺激胎儿ACTH分泌，增强胎儿ACTH对应激的反应。我们报道雌二醇增加前列腺素内过氧化物合成酶-2(PGHS-2)，我们提出雌激素与胎儿下丘脑-垂体-肾上腺（HPA）轴活性之间存在正反馈关系，这种正反馈关系依赖于胎儿大脑中PGHS活性。本研究旨在验证胎儿大脑雌激素受体阻断可降低PGHS-2表达并降低胎儿HPA轴活性的假设。方法：在研究1中，使用6只长期插管的双胎妊娠母羊。在每次怀孕中，双胞胎中的一个接受雌激素受体拮抗剂ICI 182780 （25 μ g/天；n = 6）脑室内治疗，另一个作为年龄匹配的对照组。在研究2中，从10例长期导尿的单胎胎儿中交替抽取血浆样本，直至自然分娩。结果：ICI输注引起胎儿中枢神经系统和垂体PGHS-2 mRNA丰度明显降低，以海马和垂体降低幅度最大。PGHS-1 mRNA表达变化无统计学意义。在妊娠130-134天（研究1），ICI输注没有显著改变胎儿血浆中促肾上腺皮质激素（POMC）、促肾上腺皮质激素（ACTH）或皮质醇的浓度，但在研究2中确实降低了促肾上腺皮质激素浓度的升高。结论：PGHS-2在妊娠后期胎儿脑中的表达部分受到胎儿血浆中循环雌激素的刺激。在130-134日龄的胎羊中，中枢神经系统雌激素受体阻断可降低POMC的血药浓度，但不降低HPA轴的活性。版权所有(c) 2007 S. Karger AG，巴塞尔。
Background/Aims: Both prostaglandin E 2 (PGE(2)) and estradiol stimulate fetal ACTH secretion and augment fetal ACTH responses to stress. We have reported that estradiol increases prostaglandin endoperoxide synthase-2(PGHS-2), and we have proposed that there is a positive feedback relationship between estrogen and fetal hypothalamus-pituitary-adrenal (HPA) axis activity that is dependent upon PGHS activity in the fetal brain. The present study was designed to test the hypothesis that blockade of estrogen receptors in the fetal brain decrease PGHS-2 expression and reduces fetal HPA axis activity. Methods: In study 1, six time-dated pregnant ewes with chronically-catheterized twin fetuses were used. In each pregnancy, one twin was treated intracerebroventricularly (icv) with the estrogen receptor antagonist ICI 182,780 ( 25 mu g/day; n = 6) while the other twin served as an age-matched control. In study 2, plasma samples were drawn from 10 singleton chronically-catheterized fetuses on alternating days until the time of spontaneous parturition. Results: ICI infusion caused significantly decreased PGHS-2 mRNA abundance in fetal central nervous system and pituitary, with the greatest decreases occurring in hippocampus and pituitary. There were no statistically significant changes in PGHS-1 mRNA. ICI infusion did not significantly change fetal plasma concentrations of pro-opiomelanocortin ( POMC), ACTH, or cortisol in fetuses 130-134 days gestation ( study 1) but did decrease the preparturient rise in plasma pro-opiomelanocortin concentrations in study 2. Conclusion: We conclude that PGHS-2 expression in the late-gestation fetal brain is in part stimulated by circulating estrogens in fetal plasma. Blockade of CNS estrogen receptors reduces preparturient plasma concentrations of POMC, but does not reduce fetal HPA axis activity in 130-134 day fetal sheep. Copyright (c) 2007 S. Karger AG, Basel.