The premature deposition or lysis of glycogen in livers of fetal rats injected with hydrocortisone or glucagon

Greengard, Olga; Dewey, Henry K.

doi:10.1016/0012-1606(70)90135-1

Cited by 75 publications

(33 citation statements)

References 16 publications

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“…First, the rise in endogenous IRG levels preceded the hepatic changes. Second, exogenous glucagon administered to fetal rats in utero has been shown to be capable of provoking premature glycogen degradation (46)(47)(48), increasing activities of glucose-6-phosphatase (49, 50), PEPCK (2, 51), and phosphorylase (3,50). The third suggestive line of evidence is the hypoaminoacidemic effect of exogenous glucagon in the fetus' as well as the adult (10,12).…”

Section: Methodsmentioning

confidence: 99%

Fuels, Hormones, and Liver Metabolism at Term and during the Early Postnatal Period in the Rat

Girard¹,

Cuendet²,

Marliss³

et al. 1973

J. Clin. Invest.

372

238

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A B ST R A C T The metabolic response to the first fast experienced by all mammals has been studied in the newborn rat. Levels of fuels and hormones have been compared in the fetal and maternal circulations at term. Then, after cesarean section just before the normal time of birth, sequential changes in the same parameters were quantified during the first 16 h of the neonatal period. No caloric intake was permitted, and the newborns were maintained at 370C. Activities of three key hepatic enzymes involved in glucose production were estimated.Marked differences in maternal and fetal hormones and fuels were observed. Lower levels of glucose, free fatty acids, and glycerol but higher levels of lactate, a-amino nitrogen, alanine, and glutamine were present in the fetus. Pyruvate, glutamate, and ketone bodies were not significantly different. The combination of a strikingly higher fetal immunoreactive insulin and a slightly lower immunoreactive glucagon (pancreatic) resulted in a profound elevation in the insulin-to-glucagon ratio, a finding consistent with an organism in an anabolic state.The rat at birth presents a body composition with respect to fuels available for mobilization and conversion which is dominated by carbohydrate and protein, since little fat is present. However, at birth a transient period of hypoglycemia occurred, associated with a rapid fall in insulin and rise in glucagon, causing reversal of the insulin-to-glucagon relationship toward ratios such as were observed in the mother. After a lag period, hepatic activities of phosphorylase, glucose-6-phosphatase, and phosphoenolpyruvate carboxykinase increased. Concurrent with these enzyme changes, the blood glucose returned to levels at or above those of the fetus. Interestingly, the fall observed in levels of the gluconeogenic precursors, lactate and amino acids, preceded the rise in enzyme activities and restoration of blood glucose. After 4 h, however, hypoglycemia recurred, during a period of decreasing hepatic glycogen content and blood lactate, pyruvate, and glycerol levels but of stable or increasing amino acid concentrations. Hepatic gluconeogenesis in this phase of depleted glycogen stores was insufficient to maintain euglycemia.Substrates derived from fat showed early changes of smaller magnitude. The rise in free fatty acids which occurred was less than twofold the value at birth, though this rise persisted up to 6 h. Whereas glycerol rose transiently, acetoacetate did not change and P-hydroxybutyrate concentration fell. Both ketone bodies showed a marked rise at 16 h, at a time of diminished free fatty acid levels. Plasma growth hormone, though higher in the fetal than the maternal circulation, showed no consistent change during the period of observation.The changes in levels of the endocrine pancreatic hormones at birth were appropriate in time, magnitude, and direction to be implicated as prime regulators of the metabolic response during the neonatal period in the rat.

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Section: Methodsmentioning

confidence: 99%

Fuels, Hormones, and Liver Metabolism at Term and during the Early Postnatal Period in the Rat

Girard¹,

Cuendet²,

Marliss³

et al. 1973

J. Clin. Invest.

372

238

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“…This suggests that cortico steroids are responsible for the onset of glyco gen storage and that insulin only potentiates this effect. One possibility suggested was that corticosteroids might induce some step neces sary for insulin action (7), for example, the induction of the rate-limiting enzyme glycogen synthetase (EC 2.4.1.11), the synthesis of which has been shown to be stimulated by cortisol (8).…”

Section: Discussionmentioning

confidence: 99%

Glycogen Deposition in Fetal Mouse Tissues and the Effect of Dexamethasone

Tye

Burton²

1980

Neonatology

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Glycogen in fetal mouse tissues was isolated and determined using the anthrone method on gestational days 14–19. Fetal liver showed rapid glycogen deposition after gestational day 17, reaching a value of 46.7 mg/g wet weight on day 19. Heart and placenta showed sizable glycogen stores earlier, with peak values of 21.7 and 12.8 mg/g, respectively, on day 16 which declined thereafter. Lung maintained approximately 10 mg/g days 16–19; gut and brain contained approximately 2 and 4 mg/g, respectively, days 14–19. After injection of dexamethasone into mothers on gestational day 15.5, 16 h prior to assay, the glycogen content of liver increased approximately tenfold, while placental glycogen declined. This indicates that corticosteroids merely accelerate the pattern observed in the normal course of gestation.

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“…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.…”

mentioning

confidence: 99%

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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The premature deposition or lysis of glycogen in livers of fetal rats injected with hydrocortisone or glucagon

Cited by 75 publications

References 16 publications

Fuels, Hormones, and Liver Metabolism at Term and during the Early Postnatal Period in the Rat

Fuels, Hormones, and Liver Metabolism at Term and during the Early Postnatal Period in the Rat

Glycogen Deposition in Fetal Mouse Tissues and the Effect of Dexamethasone

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

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