Corticotrophin and Cortisol Concentrations in the Plasma of the Chronically Catheterised Sheep Fetus

Alexander, D. Pauline; Britton, H.G.; Nixon, D. A.; Ratcliffe, J G; Redstone, D.

doi:10.1159/000240600

Cited by 17 publications

(10 citation statements)

References 5 publications

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“…Cortisol infusion substantially increased plasma cortisol levels in the experimental twin, whereas plasma cortisol in the control twin remained unchanged. Plasma cortisol levels reached in the test twin were similar to cortisol concentrations found in newborn lambs at birth (25).…”

Section: Resultssupporting

confidence: 74%

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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: Resultssupporting

confidence: 74%

“…Four sets of twins were studied at 118 d, which is near the beginning of the 3rd trimester (term, 145 d), and three sets were studied at 138 d of gestation, before the surge in plasma cortisol levels that occurs just before birth (24,25). Sets of twin fetuses were studied so that a paired control was included in each experiment.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 1991

Pediatr Res

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“…The basal fetal plasma ACTH levels reported here are not only considerably lower than the values reported in studies using acutely exteriorized lambs (5,6,32,33), but also lower than the values in chronically catheterized fetal sheep (24,25,(34)(35)(36)(37)(38). Indeed, in our chronically catheterized animals, the mean resting ACTH concentration was slightly lower in fetal than in maternal plasma and was similar to basal ACTH values observed by others in adult animals (12,(14)(15)(16)(17)(35)(36)(37)(38)(39).…”

Section: Resultssupporting

confidence: 63%

Developmental Aspects of the Pituitary-Adrenal Axis Response to Hemorrhagic Stress in Lamb Fetuses In Utero

Rose¹,

Macdonald²,

Heymann³

et al. 1978

J. Clin. Invest.

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A B S T R A C T Plasma ACTH and corticosteroid concentrations were measured by radioimmunoassay in chronically catheterized fetuses of 32 pregnant sheep. Fetal plasma ACTH levels 38+5 pglml (means±SEM) were slightly (P < 0.05) lower than maternal 54±4 pg/ml levels. No general rise in fetal plasma ACTH concentration was noted before 140 days gestation; however, fetal plasma corticoid levels began to increase after about 125 days. This suggested that an increase in fetal adrenal responsiveness to endogenous ACTH occurred during gestation.Hemorrhage of 15% of estimated blood volume decreased mean arterial pressure from 54+3 to 36±3 torr and increased plasma ACTH from 30±5 to 130 ±30 pg/ml in fetuses older than 0.80 gestation. In fetuses younger than 0.67 gestation, 15% hemorrhage caused no change in plasma ACTH levels despite a significant fall in mean arterial pressure. This suggests that system(s) subserving the ACTH response to mild hemorrhage are either absent or nonfunctional in the younger fetuses. The hemorrhage-induced increase in plasma ACTH levels was associated with a small rise in plasma corticoids in fetuses younger than 0.94 gestation. In older fetuses, a similar increase in plasma ACTH was associated with a pronounced increase in plasma corticoid levels. This also suggests that an increase in adrenal responsive-

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“…We do not know whether plasma catecholamine concentrations increased in our preparation, but combined ventricular output did not change when the umbilical cord was occluded. Another important difference between normal birth and our study is the presence of prenatal increases in plasma cortisol and thyroid hormone concentrations that occur just prior to normal delivery (30,31). Breall et al (32) have shown that fetal sheep subjected to thyroidectomy about 2 wk prior to delivery do not demonstrate the increases in cardiac output and heart rate which occur in normal lambs after delivery (5).…”

Section: Central Blood Flow During Birth Events 563mentioning

confidence: 55%

Effects of Birth-Related Events on Central Blood Flow Patterns

1987

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ABSTRACT. We determined the effects of three components of the birth process on central blood flow patterns in fetal sheep. We instrumented 16 fetal sheep at 133.0 f 1.2 days gestation, inserting various intravascular catheters, intubating the trachea, and placing an inflatable balloon around the umbilical cord. After 2-3 days, we determined central blood flow patterns using radionuclidelabeled microspheres under control conditions, during positive pressure ventilation without oxygenation, during ventilation with 100% Oz, and after umbilical cord occlusion. The foramen ovale right to left shunt was essentially abolished, decreasing from 102 f 48 to 66 f 40 ml/min/ kg with ventilation, and to only 13 f 10 ml/min/kg with oxygenation. The ductus arteriosus right to left shunt decreased progressively, from a control level of 224 2 64 to 6 f 10 ml/min/kg after umbilical cord occlusion. A ductus arteriosus left to right shunt appeared with oxygenation (41 f 26 ml/min/kg) and increased to 65 f 43 ml/ min/kg after cord occlusion. Left ventricular output increased progressively a s a percentage of combined ventricular output (from a control value of 34.8 to 59.5% after cord occlusion), and increased absolutely with ventilation (from 134 f 44 to 211 f 87 ml/min/kg). However, right ventricular output decreased (from a control value of 258 f 75 to 144 f 36 ml/min/kg after cord occlusion) so that combined ventricular output did not change. Although the transition from the fetal to neonatal circulatory pattern was accomplished by simulating these three components of the birth process, none is alone responsible for the large increase in combined ventricular output normally seen a t birth. The adaptation of the fetus to extrauterine life involves numerous processes that occur rapidly. Paramount among these is the change in the pattern of circulation of blood. The fetal circulation is characterized by the presence of central shunts that direct systemic venous return to the systemic arterial circulation ( Fig. 1): the foramen ovale directs the more highly oxygenated umbilical venous blood from the right atrium to the left heart to supply oxygen to the heart, brain, and other organs, and the ductus arteriosus directs the less oxygenated right ventricular output via the descending aorta to the placenta for oxygen uptake. The right ventricle ejects about 50% more blood than the left ventricle in the sheep fetus (1). As part of the transition from fetal to neonatal life, these central blood flow patterns change abruptly. The right to left shunts through the foramen ovale (2) and through the ductus arteriosus (3) cease rapidly, and a transient left to right shunt occurs until the ductus arteriosus closes fully within a few hours after birth (3,4). The two ventricles eject the same volumes once the ductus arteriosus does close. Associated with the increased oxygen requirements after birth, left ventricular output increases 2-to 21/2-fold (5, 6).The specific factors that cause this dramatic change in central blood flow patterns and thei...

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Corticotrophin and Cortisol Concentrations in the Plasma of the Chronically Catheterised Sheep Fetus

Cited by 17 publications

References 5 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

Developmental Aspects of the Pituitary-Adrenal Axis Response to Hemorrhagic Stress in Lamb Fetuses In Utero

Effects of Birth-Related Events on Central Blood Flow Patterns

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