Negative Regulation of Angiotensinogen Gene Expression by Glucocorticoids in Fetal Sheep Liver

Al, Olson; Je, Robillard; Ct, Kisker; Ba, Smith; Perlman, Signe

doi:10.1203/00006450-199109000-00011

Cited by 15 publications

(14 citation statements)

References 23 publications

(29 reference statements)

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“…One may suggest that cortisol increases the production of angiotensinogen (renin substrate) to prevent changes in plasma A11 levels in face of a decrease in renin production. Previous studies in sheep, however, have shown that fetal cortisol infusion does not produce changes in circulating angiotensinogen (50) and is, in fact, associated with a decrease in liver angiotensinogen mRNA levels (22), in contrast to previous findings in adults (51,52). An alternative hypothesis would be that cortisol infusion in fetal sheep increases converting enzyme activity and consequently the rate of conversion of angiotensin I to AII, as previously suggested (53).…”

Section: Discussioncontrasting

confidence: 54%

“…Indeed, glucocorticoid has been shown to downregulate both AT, and AT2 receptors in pancreatic acinar cells (44) and to produce down-regulation of glomerular A11 receptor in rats (45). Another possibility is that the decreased expression of renal AT, gene as a function of cortisol concentration is indirect and depends on factors interacting with specific DNA sequences on the glucocorticoid regulatory elements, as previously suggested (22,46). One may also speculate that developmental changes in the physiochemical nature of glucocorticoid receptors (47,48) affect the hormonal responsiveness of certain genes during fetal life.…”

Section: Discussionmentioning

confidence: 85%

“…Studies were performed in fetal sheep and newborn lambs of Dorset and Suffolk mixed breeding, obtained from a local source. The gestational ages of the fetuses were based on the induced ovulation technique as previously described (20) Anesthesia and surgery of the ewe and fetus were performed as previously described (19,21,22). Briefly, the ewe was fasted for 24 h before surgery and anesthetized using a mixture of halothane (I%), oxygen (33%), and nitrous oxide (66%).…”

Section: Methodsmentioning

confidence: 99%

“…Hematocrit was determined in duplicate using a micrometer caliper. RIA, previously established in our laboratory, were used to measure plasma cortisol (22), plasma A11 (25) concentrations, and PRA (25,26).…”

Section: Methodsmentioning

confidence: 99%

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Ontogenic Changes and Regulation of Renal Angiotensin II Type 1 Receptor Gene Expression during Fetal and Newborn Life

et al. 1994

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Factors regulating the expression of the angiotensin I1 subtype 1 (AT,) receptor during fetal life have not been investigated previously. The present study was designed 1) to characterize the ontogeny of AT, receptor gene expression in the kidney of fetal and newborn sheep and 2) to determine the influence of both glucocorticoids and renal nerves in modulating AT, gene expression during fetal life and during the transition from fetal to newborn life. We first isolated and cloned a PCR product that has 98 and 94% homology with the cDNA encoding the bovine and pig AT, receptors, respectively, and 99 and 98% homology with the corresponding deduced protein sequences. Probing with this cDNA, we demonstrated that renal AT, mRNA expression did not change significantly during the last trimester of gestation in fetal sheep or immediately after birth but decreased significantly 10 d after birth. We also demonstrated that renal denervation in the fetus had no effect on renal AT, gene expression in 24-h-old newborn lambs. On the other hand, we observed in 130-d twin fetuses that a continuous intraperitoneal infusion (1 mL/h) of cortisol (3 mg/h or 6.2 p,mol/h) for 48 h in one of the twins increased the fetal plasma cortisol concentration from 32.0 + 7.1 to 1126 r 231 nmol/L and produced a significant decrease ( p < 0.005) in renal AT, gene expression compared with the control twin receiving an intraperitoneal infusion of 0.9% NaCl. In summary, this study demonstrates that renal AT, gene expression is elevated during fetal life and decreases after birth. It is also shown that glucocorticoids, but not renal nerves, contribute to the regulation of renal AT, gene expression during development. (Pediatr Res 36: 755-762, 1994)Abbreviations RAS, renin-angiotensin system AII, angiotensin I1 AT,, angiotensin I1 subtype 1 receptor AT,, angiotensin I1 subtype 2 receptor PCR, polymerase chain reaction RSNA, renal sympathetic nerve activity PRA, plasma renin activity rRNA, ribosomal RNA It has become apparent that the physiologic role of the RAS changes during embryonic and fetal maturation (1-4). Early during development, the RAS exerts a major influence o n cellular growth and organ differentiation (3-6). It is only later during fetal life that the RAS becomes an important modulator of blood pressure and distinct A11 receptor subtypes (AT, and AT,) (3, 9, 10). The AT, receptor subtype is expressed early during embryonic life in the rat (11,12), predominates in the fetal mesenchyme (3), and shows a marked decrease in expression during fetal and postnatal maturation (3). On the other hand, the AT, receptor subtype appears later during fetal development in the rat (3, 9, 10) and seems t o b e localized mainly in areas related t o blood pressure regulation and fluid homeostasis (3). Recent studies in rats have also shown that the AT, receptor gene is expressed in the fetal kidney, liver, adrenal, and heart and that the expression of this gene is developmentally regulated (9, lo), in agreement with previous A11 radioligand and in situ rece...

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Section: Discussioncontrasting

confidence: 54%

Section: Discussionmentioning

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Ontogenic Changes and Regulation of Renal Angiotensin II Type 1 Receptor Gene Expression during Fetal and Newborn Life

et al. 1994

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“…Hematocrit was determined in duplicate using a meter caliper. RIA, previously established in our laboratory, were used to measure plasma cortisol (19) and plasma A11 (20) concentrations and PRA (20,21).…”

Section: Animalsmentioning

confidence: 99%

Differential Gene Expression and Regulation of Renal Angiotensin II Receptor Subtypes (AT1 and AT2) during Fetal Life in Sheep

et al. 1995

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Previous studies have shown that angiotensin I1 subtype 2 (AT,) receptors appear early during renal embryonic development. Factors involved in the regulation of AT, receptors during renal development, however, have not been investigated. The present study was designed 1 ) to characterize the ontogeny of renal AT, gene expression during the last half of gestation in fetal sheep and newborn lambs, 2) to compare changes in AT, and AT, gene expression during renal development, 3) to determine the influence of A11 in modulating renal AT, and AT, gene expression during fetal life, and 4) to characterize the role of cortisol in modulating renal AT, gene expression during the last trimester of gestation in fetal sheep. To perform these studies, we first isolated and cloned a polymerase chain reaction product that has 92 and 90% homology with the cDNA encoding the human and rat AT, receptors, respectively. Using this sheep AT, cDNA probe, we demonstrated that the sheep AT, gene was encoded in a single locus. In addition, we showed that renal AT, mRNA expression was high early during fetal life (60-90-d gestation) and decreased rapidly thereafter. In contrast, the expression of renal AT, receptor gene was low at 60-d gestation and increased during the last trimester of gestation. We found that a continuous i.v. infusion (1 mL/h) of A11 (9.5 nM/h) for 24 h, which raised plasma A11 levels from 84 t-9 pg/mL to 210 i-21 pg/mL, decreased the expression of both renal AT, and AT, genes in third trimester fetal sheep. On the other hand, we observed that cortisol, known to decrease AT, gene expression in the fetus, had no effect on AT, gene expression. In summary, this study demonstrates that AII, but not glucocorticoids, contributes to the regulation of renal AT, gene expression during development and that there is differential regulation of AT, and AT, receptors. (2), and the expression of renin, angiotensinogen, and angiotensinconverting enzyme genes appear to be developmentally regulated (3-6).It has been suggested that A11 is implicated in the regulation of renal function (1) and renal growth (7) during development.The biologic effects of A11 are mediated by two distinct specific receptors (AT, and AT,) located in the plasma membrane of different tissues (8). Studies in rats (9, 10) and sheep (11) have shown that the expression of kidney AT, receptor mRNA is developmentally regulated. In the sheep, renal AT, mRNA expression is elevated during the last trimester of gestation and decreases during the second postnatal week (1 1).In the rat, the expression of renal AT, receptor mRNA is also higher in immature than in adult animals (12). Discrete expression of AT, receptor has been observed as early as 2 d of postnatal age in rat immature glomeruli (10).Both in situ hybridization and autoradiographic studies have also shown that AT, receptors are present in the fetal mesenchyme (13), in the mesonephros before its involution (14), in

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Angiotensinogen

Tewksbury

2000

Comprehensive Physiology

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The sections in this article are: Primary Structure Kinetics of the Renin‐Angiotensinogen Reaction Regulation Hormonal Regulation Transcriptional and Translational Regulation In Vivo Manipulation of Angiotensinogen Gene Expression Tissue Renin–Angiotensin Systems Brain Pituitary Kidney Adrenal Heart Vascular Tissue Adipose Tissue Angiotensinogen and the Acute‐Phase Reaction Angiotensinogen and Essential Hypertension Angiotensinogen and Preeclampsia Angiotensinogen and Heart Disease Summary

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Negative Regulation of Angiotensinogen Gene Expression by Glucocorticoids in Fetal Sheep Liver

Cited by 15 publications

References 23 publications

Ontogenic Changes and Regulation of Renal Angiotensin II Type 1 Receptor Gene Expression during Fetal and Newborn Life

Ontogenic Changes and Regulation of Renal Angiotensin II Type 1 Receptor Gene Expression during Fetal and Newborn Life

Differential Gene Expression and Regulation of Renal Angiotensin II Receptor Subtypes (AT1 and AT2) during Fetal Life in Sheep

Angiotensinogen

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