Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Potential mechanisms underlying prenatal programming of hypertension in adult life were investigated using a rat model in which maternal protein intake was restricted to 9% vs. 18% casein (control) during pregnancy. Maternal low protein (MLP) offspring exhibit glucocorticoid-dependent raised systolic blood pressure throughout life (20-30 mm Hg above the control). To determine the molecular mechanisms underlying the role of alterations in glucocorticoid hormone action in the prenatal programming of hypertension in MLP offspring, tissues were analyzed for expression of the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11betaHSD1, 11betaHSD2, and corticosteroid-responsive Na/K-adenosine triphosphatase alpha1 and beta1. GR protein (95 kDa) and messenger RNA (mRNA) expression in kidney, liver, lung, and brain was more than 2-fold greater in MLP vs. control offspring during fetal and neonatal life and was more than 3-fold higher during subsequent juvenile and adult life (P < 0.01). This was associated with increased levels of Na/K-adenosine triphosphatase alpha1- and beta1-subunit mRNA expression. Levels of MR gene expression remained unchanged. Exposure to the MLP diet also resulted in markedly reduced levels of 11betaHSD2 expression in the MLP placenta on days 14 and 20 of gestation (P < 0.001), underpinning similar effects on 11betaHSD2 enzyme activity that we reported previously. Levels were also markedly reduced in the kidney and adrenal of MLP offspring during fetal and postnatal life (P < 0.001). This programmed decline in 11betaHSD2 probably contributes to marked increases in glucocorticoid hormone action in these tissues and potentiates both GR- and MR-mediated induction of raised blood pressure. In contrast, levels of 11betaHSD1 mRNA expression in offspring central and peripheral tissues remained unchanged. In conclusion, we have demonstrated that mild protein restriction during pregnancy programs tissue-specific increases in glucocorticoid hormone action that are mediated by persistently elevated expression of GR and decreased expression of 11betaHSD2 during adult life. As glucocorticoids are potent regulators not only of fetal growth but also of blood pressure, our data suggest important potential molecular mechanisms contributing to the prenatal programming of hypertension by maternal undernutrition in the rat.
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PMID:The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11beta-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero. 1141 3

Changes in adrenal corticosteroid secretion result in changes in lung liquid production in the late-gestation fetus. To test for the presence of mineralocorticoid receptor (MR) in fetal pulmonary epithelium, lungs from fetal sheep of 120 to 130 days' gestation (term about 148 days) were collected and frozen for identification of mRNA for MR in homogenates by reverse transcriptase polymerase chain reaction (RT-PCR) or for determination of 3H-cortisol binding at MR. Other samples of fetal lungs were fixed for localization of MR and Na+, K+ adenosine triphosphatase (ATPase) alpha by immunohistochemistry. MR mRNA was identified in lung tissue from fetuses and newborn lambs, but not from pregnant ewes; MR-regulated genes, including SGK1 and ENaCalpha were also expressed in fetal and newborn lungs. Immunoreactive MR was found in pulmonary epithelial cells and to be colocalized with Na+, K+ ATPase alpha in many sites. These results indicate that the molecular apparatus for mineralocorticoid-stimulated lung liquid reabsorption is present in epithelium by 120 days' gestation.
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PMID:Mineralocorticoid receptor expression in late-gestation ovine fetal lung. 1569 2