Hepatic Angiotensinogen Gene Regulation in the Fetal and Pregnant Rat1

Ad, Everett; Rl, Chevalier; Gomez, R. Ariel

doi:10.1203/00006450-199109000-00010

Cited by 17 publications

(8 citation statements)

References 24 publications

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“…The decrease in angiotensinogen mRNA in fetal sheep liver after cortisol stimulation differs from the results of a previous study in fetal rats (26). In that study (26), administration of pharmacologic doses of dexamethasone to pregnant rats for 5 consecutive d increased fetal hepatic angiotensinogen mRNA levels but had no effect on fetal heart, kidney, and brain angiotensinogen gene expression.…”

Section: Discussioncontrasting

confidence: 55%

“…In that study (26), administration of pharmacologic doses of dexamethasone to pregnant rats for 5 consecutive d increased fetal hepatic angiotensinogen mRNA levels but had no effect on fetal heart, kidney, and brain angiotensinogen gene expression. Reasons for the differences between the present study and the study by Everett et al (26) are not clear but may represent either a different species' response to the drugs, different responses to cortisol versus dexamethasone, or the use of physiologic versus pharmacologic dosages of steroid.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 1991

Pediatr Res

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ABSTRACT. The effect of glucocorticoids in regulating liver angiotensinogen gene expression was studied in chronically instrumented fetal sheep during the last trimester of gestation and was compared with the expression of other hepatic genes (prothrombin, factor IX, and albumin). Four sets of twins were studied at 118 d of gestation, and three sets were studied at 138 d of gestation (term, 145 d). One of each set of twins was infused intraperitoneally with cortisol (5 pmol.mL-'.h-') for 48 h, whereas the other twin received the same volume (1 mL/h) of normal saline. Plasma cortisol concentration increased from 0.32 f 0.12 and 2.7 f 0.12 nmo1/100 mL to 44.2 f 20.0 and 37.7 f 8.2 nmo1/100 mL in 118-and 138-d fetuses, respectively, during the cortisol infusion; no changes were observed in fetuses infused with saline alone. At the end of the infusion period, the animals were anesthetized, the fetal liver was removed, and total cellular RNA was isolated and probed for angiotensinogen, prothrombin, factor IX, and albumin. The results demonstrated that cortisol infusion decreased angiotensinogen mRNA by 61% in 138-d fetuses and albumin mRNA expression by 2.4-fold in 118-d fetuses and by 3.4-fold in 138-d fetuses. On the other hand, cortisol had no effect on fetal factor IX gene expression but increased prothrombin mRNA levels by 65% in 118-d fetuses and 62% in 138-d fetuses. Taken together, our results suggest that, during fetal life, angiotensinogen gene expression is negatively regulated by glucocorticoids. This effect is not universal because cortisol increases fetal prothrombin gene expression. (Pediatr Res 30: 256-260, 1991) Abbreviations SSPE, sodium chloride, sodium phosphate, EDTA creases during the last trimester of gestation but has been shown to decrease in the 1st wk after birth (5).Studies in mature rats have demonstrated that multiple factors, including glucocorticoids, can modulate liver angiotensinogen gene expression (6-9). Less is known about regulation of angiotensinogen mRNA levels in the fetus, but it has been suggested that glucocorticoid hormones play an important role in organ maturation and enzyme induction during fetal life (10, 11). In vitro studies with cultured rat fetal hepatocytes (12) have shown that addition of dexamethasone to culture media causes fetal hepatocytes to express adult levels of mRNA for albumin, tyrosine aminotransferase, and transfemn while decreasing the level of a-fetoprotein mRNA. Information about glucocorticoid effects on gene expression in fetal liver in vivo is more limited and differs from results obtained in vitro. Johnson et al. (13) have shown that tyrosine aminotransferase mRNA is not affected by glucocorticoids in near-term fetal rats but that hormone responsiveness develops postnatally.In an effort to determine if glucocorticoids play a role in the expression of liver angiotensinogen gene during fetal life, we studied the effect of cortisol on the hepatic expression of angiotensinogen gene in chronically instrumented fetal sheep. We also compared the e...

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Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

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

et al. 1991

Pediatr Res

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“…A positive feedback has been described in adult rat liver whereby high levels of AnglI increase angiotensinogen gene expression (40,41 ). In the fetal liver angiotensinogen mRNA levels are very low before 20 d gestation, increasing immediately after birth to adult levels (5,42 of angiotensinogen expression in the fetal liver, thus initiating the positive feedback loop described for the adult animal.…”

Section: Discussionmentioning

confidence: 99%

Ontogeny of type 1 angiotensin II receptor gene expression in the rat.

Tufro-McReddie¹,

Harrison²,

Everett³

et al. 1993

J. Clin. Invest.

126

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To determine whether the expression of the type 1 angiotensin II receptor (AT1) gene is developmentally regulated and whether the regulation is tissue specific, AT1 mRNA levels were determined by Northern blot analysis in livers and kidneys from fetal, newborn, and adult rats, using a 1133-bp rat AT1 cDNA. In the liver, AT, mRNA levels increased fivefold from 15 d gestation to 5 d of age. Liver AT, mRNA levels at 5 d of age were similar to those of adult rats. In the kidney, AT, mRNA levels were higher in immature than in adult animals. The intrarenal distribution of AT1 mRNA was assessed by in situ hybridization to a 35S-labeled 24 residues oligonucleotide complementary to rat AT1 mRNA. In the adult, AT1 mRNA was present in glomeruli, arteries, and vasa recta, whereas in the newborn AT1 mRNA was observed also over the nephrogenic area of the cortex.We conclude that: (a) fetal kidney and liver express the AT1 gene; (b) the AT1 gene expression is developmentally regulated in a tissue-specific manner; (c) during maturation, localization of AT1 mRNA in the kidney shifts from a widespread distribution in the nephrogenic cortex to specific sites in glomeruli, arteries, and vasa recta, suggesting a role for the angiotensin receptor in nephron growth and development. (J. Clin. Invest. 1993. 91:530-537.)

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“…Importantly, in adult rats, glucocorticoids regulate all of the principle components of the RAS, including renin secretion (17), angiotensinogen synthesis (16), ANG-converting enzyme activity (43), ANG II (56), and mineralocorticoid receptor expression (55). Furthermore, in the fetal rat, hepatic angiotensinogen mRNA levels are regulated by glucocorticoids (26).…”

mentioning

confidence: 99%

Glucocorticoid exposure in late gestation in the rat permanently programs gender-specific differences in adult cardiovascular and metabolic physiology

O’Regan¹,

Kenyon²,

Seckl³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

206

182

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.-Glucocorticoid overexposure in utero may underlie the association between low birth weight and subsequent development of common cardiovascular and metabolic pathologies. Previously, we have shown that prenatal dexamethasone (DEX) exposure in rat reduces birth weight and programs the hypothalamic-pituitary axis and fasting and postprandial hyperglycemia in adult males and hypertension in adult males and females. This study aimed to determine 1) whether there were gender differences in prenatal DEX-programmed offspring, and 2) whether the renin-angiotensin system (RAS) plays a role in the programming of hypertension. Rats exposed to DEX in utero (100 g ⅐ kg Ϫ1 ⅐ day Ϫ1 from embryonic days 14 -21) were of lower birth weight (by 12%, P Ͻ 0.01) and displayed full catch-up growth within the first month of postnatal life. DEX-treated male offspring in adulthood selectively displayed elevated plasma adrenocorticotropic hormone (by 221%) and corticosterone (by 188%, P Ͻ 0.05), postprandial insulin-glucose ratios (by 100%, P Ͻ 0.05), and hepatic expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (by 38%, P Ͻ 0.05). Conversely, DEXprogrammed females were hypertensive (by 11%, P Ͻ 0.05), with elevated hepatic angiotensinogen mRNA expression (by 9%, P Ͻ 0.05), plasma angiotensinogen (by 61%, P Ͻ 0.05), and renin activity (by 88%, P Ͻ 0.05). These findings demonstrate that prenatal glucocorticoids program adulthood cardiovascular and metabolic physiology in a gender-specific pattern, and that an activated RAS may in part underlie the hypertension associated with prenatal DEX programming.glucocorticoids; birth weight; hypothalamic-pituitary axis; glucose homeostasis; blood pressure; renin-angiotensin system EPIDEMIOLOGICAL STUDIES in many human populations suggest that the common metabolic and cardiovascular disorders of adult life are influenced by intrauterine factors (7,19). In particular, low birth weight (assumed to be a marker for an adverse intrauterine environment) is associated with a higher frequency of hypertension (5), type 2 diabetes (42), and death from ischemic heart disease in adulthood (7,19,42). The phenomenon of prenatal "programming" has been advanced to explain these findings whereby a factor, acting during a discrete developmental "window," alters the maturation of specific organs, permanently altering their function (6, 10). The systems affected are determined by their particular vulnerability at the time of exposure (54). Although the precise mechanisms underpinning prenatal programming remain elusive, we hypothesized that excessive fetal exposure to glucocorticoids might be important on the basis of the documented effects of antenatal glucocorticoid administration to reduce birth weight and alter the trajectory of maturation of specific fetal organs (24). Glucocorticoid excess in adults or children causes many of the features of the "small baby syndrome." In rats, we and others have shown that prenatal exposure to the synthetic glucocorticoid dexamethasone (DEX) or to endogenous...

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Hepatic Angiotensinogen Gene Regulation in the Fetal and Pregnant Rat1

Cited by 17 publications

References 24 publications

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

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

Ontogeny of type 1 angiotensin II receptor gene expression in the rat.

Glucocorticoid exposure in late gestation in the rat permanently programs gender-specific differences in adult cardiovascular and metabolic physiology

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