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首页> 外文期刊>Neonatology >Is the fetal lung a mineralocorticoid receptor target organ? Induction of cortisol-regulated genes in the ovine fetal lung, kidney and small intestine.
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Is the fetal lung a mineralocorticoid receptor target organ? Induction of cortisol-regulated genes in the ovine fetal lung, kidney and small intestine.

机译:胎儿肺部是盐皮质激素受体的靶器官吗?在绵羊胎儿的肺,肾和小肠中诱导皮质醇调节基因。

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摘要

BACKGROUND: Lung, kidney and small intestine are involved in fetal volume regulation and amniotic fluid secretion and play a pivotal role in the transition from intrauterine to extrauterine life. OBJECTIVE: This study was performed to determine the ontogeny of mineralocorticoid receptors (MR) and glucocorticoid receptors (GR), and of MR- and GR-regulated genes and proteins, serum and glucocorticoid-induced kinase (Sgk-1), epithelial sodium channel (ENaC alpha), and Na,K-ATPase alpha1. METHODS: Lung, renal cortex and medulla, and small intestine were collected from fetuses at 80, 100, 120, 130 and 145 days' gestation and from day 1 and 7 neonatal lambs. Real-time PCR was performed to determine mRNA concentration for MR, GR, the 11 beta-hydroxysteroid dehydrogenases (11 beta-HSD1 and 2), Sgk-1, ENaC alpha, and Na,K-ATPase alpha1. Protein expression of ENaC alpha and Na,K-ATPase alpha1 in whole cell and membrane fractions was determined by immunoblotting. RESULTS: Expression of corticosteroid-induced genes in renal cortex increases at term; in small intestine the induction occurs postnatally. In contrast, in lung expression of MR and GR mRNAs were greater at 100 days to term than postnatally and 11 beta-HSD1 peaked at 145 days; the corticosteroid-induced genes also increased prenatally: Sgk-1 and ENaC alpha increased by 120 days, peaking at 145 days, and Na,K-ATPase alpha1 was greatest at 130 days. CONCLUSIONS: The expression of high levels of MR and 11 beta-HSD1 in preterm fetal lung suggest low endogenous fetal cortisol may exert actions at the high affinity MR in vivo, leading to increases in expression of sodium channels important in the regulation of lung liquid secretion and reabsorption.
机译:背景:肺,肾和小肠参与胎儿体积调节和羊水分泌,在从子宫内到子宫外生活的过渡中起着关键作用。目的:本研究旨在确定盐皮质激素受体(MR)和糖皮质激素受体(GR)以及MR和GR调控的基因和蛋白质,血清和糖皮质激素诱导的激酶(Sgk-1),上皮钠通道的存在(ENaC alpha)和Na,K-ATPase alpha1。方法:从80、100、120、130和145天妊娠的胎儿以及第1天和第7天的新生羔羊收集胎儿的肺,肾皮质,延髓和小肠。进行实时PCR以确定MR,GR,11种β-羟类固醇脱氢酶(11β-HSD1和2),Sgk-1,ENaCα和Na,K-ATPaseα1的mRNA浓度。通过免疫印迹测定全细胞和膜级分中ENaCα和Na,K-ATPaseα1的蛋白表达。结果:足月肾皮质中皮质类固醇诱导基因的表达增加。在小肠中,诱导发生在出生后。相比之下,足月100天时肺中MR和GR mRNA的表达要比出生后高,并且11个β-HSD1在145天达到峰值。皮质类固醇诱导的基因在出生前也增加:Sgk-1和ENaCα增加120天,在145天达到峰值,而Na,K-ATPase alpha1在130天最大。结论:早产胎儿肺中高水平的MR和11β-HSD1的表达表明低内源性胎儿皮质醇可能在体内对高亲和力MR起作用​​,从而导致在调节肺液分泌中重要的钠通道表达增加和重吸收。

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