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首页> 外文期刊>American Journal of Physiology >Cortisol stimulates proliferation and apoptosis in the late gestation fetal heart: differential effects of mineralocorticoid and glucocorticoid receptors.
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Cortisol stimulates proliferation and apoptosis in the late gestation fetal heart: differential effects of mineralocorticoid and glucocorticoid receptors.

机译:皮质醇刺激妊娠晚期胎儿心脏的增殖和凋亡:盐皮质激素和糖皮质激素受体的不同作用。

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摘要

We have previously found that modest chronic increases in maternal cortisol result in an enlarged fetal heart. To explore the mechanisms of this effect, we used intrapericardial infusions of a mineralocorticoid receptor (MR) antagonist (canrenoate) or of a glucocorticoid receptor (GR) antagonist (mifepristone) in the fetus during maternal infusion of cortisol (1 mg?kg~-1?day~-1). We have shown that the MR antagonist blocked the increase in fetal heart weight and in wall thickness resulting from maternal cortisol infusion. In the current study we extended those studies and found that cortisol increased Ki67 staining in both ventricles, indicating cell proliferation, but also increased active caspase-3 staining in cells of the conduction pathway in the septum and subendocardial layers of the left ventricle, suggesting increased apoptosis in Purkinje fibers. The MR antagonist blocked the increase in cell proliferation, whereas the GR antagonist blocked the increased apoptosis in Purkinje fibers. We also found evidence of activation of caspase-3 in c-kit-positive cells, suggesting apoptosis in stem cell populations in the ventricle. These studies suggest a potentially important role of cortico-steroids in the terminal remodeling of the late gestation fetal heart and suggest a mechanism for the cardiac enlargement with excess corticoste-roid exposure.
机译:我们先前发现母体皮质醇的适度慢性增加会导致胎儿心脏扩大。为了探索这种作用的机制,我们在母体输注皮质醇(1 mg?kg〜-)期间向胎儿心内注射了盐皮质激素受体(MR)拮抗剂(canrenoate)或糖皮质激素受体(GR)拮抗剂(mifepristone)。 1?day〜-1)。我们已经表明,MR拮抗剂阻止了母体皮质醇输注引起的胎儿心脏重量和壁厚的增加。在本研究中,我们扩展了这些研究,发现皮质醇增加了两个心室的Ki67染色,表明细胞增殖,但同时也增加了左心室的隔膜和心内膜下层传导通路的细胞中的活性caspase-3染色,浦肯野纤维的凋亡。 MR拮抗剂阻止细胞增殖的增加,而GR拮抗剂阻止浦肯野纤维的凋亡增加。我们还发现了c-kit阳性细胞中caspase-3活化的证据,提示心室干细胞群体发生凋亡。这些研究表明皮质类固醇在妊娠晚期胎儿心脏的终末重塑中具有潜在的重要作用,并提出了皮质类固醇激素暴露过多导致心脏扩大的机制。

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