Glucocorticoids and the preparation for life after birth: are there long-term consequences of the life insurance?

Fowden, Abigail L.; Li, Juan; Forhead, Alison J.

doi:10.1079/pns19980017

Cited by 422 publications

(409 citation statements)

References 82 publications

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“…CNP is inhibited by catabolic interventions such as glucocorticoid administration (7) and caloric restriction (9), which also reduces circulating CNP forms in the fetal lamb (10). In this study, the increase in fetal plasma cortisol concentrations was much smaller than that normally associated with slowed fetal growth before birth (19) or demonstrated slow fetal growth earlier in gestation (20). Consistent with this, we found no changes in fetal growth, even when measured using the sensitive technique of daily changes in fetal girth (15,16).…”

Section: Discussionmentioning

confidence: 72%

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Effect of Cortisol on C-Type Natriuretic Peptide in Ovine Pregnancy: Differential Responses in Fetal and Placental Tissues

et al. 2010

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ABSTRACT:We have used aminoterminal pro C-type natriuretic peptide (NTproCNP)-a stable marker of CNP secretion-to study the effect of cortisol on CNP secretion and fetal growth. In ovine pregnancy, maternal plasma NTproCNP (largely sourced from the placenta) increases at the end of the first trimester and then decreases abruptly preterm during the phase of fetal surge in cortisol secretion. Postulating that increases in cortisol, as occurs in the fetal or maternal circulation in late pregnancy, will reduce CNP secretion, we studied the fetal and maternal responses in NTproCNP to sustained low-dose infusions of cortisol (1.2 mg/d/kg for 11 d) delivered to the fetus from d 117 gestation. Fetal plasma NTproCNP was progressively reduced during fetal cortisol infusions, whereas fetal girth growth was unchanged. In contrast, maternal NTproCNP was unaffected by cortisol. We conclude that fetal but not placental tissue production of CNP is reduced by small increments in fetal cortisol. Failure to reduce maternal NTproCNP may relate to the continuing presence of the placental barrier to cortisol at this stage of pregnancy. (Pediatr Res 68: 462-465, 2010) C -type natriuretic peptide (CNP) is an important growth factor expressed in a wide range of tissues (1) during development (2) and postnatal life (3). Although shown to be essential to postnatal linear growth in both rodents (4) and humans (5), CNP production has also been found to correlate strongly with linear growth velocity in lambs and throughout all phases of linear growth in humans (6 -8). In rapidly growing lambs, catabolic interventions such as caloric restriction (9) and high doses of glucocorticoids (7), well-recognized inhibitors of linear growth, rapidly and reversibly reduce circulating forms of CNP and markers of bone formation. Similar reductions in CNP forms occur in the fetus during maternal caloric restriction (10) or glucocorticoid administration (6). However, the effect of physiological increments in fetal cortisol on CNP synthesis is unknown.Recent studies of ovine pregnancy show that both CNP and the bio inactive aminoterminal fragment of pro CNP 1-103 (NTproCNP) (11) are secreted by the placenta and circulate at high concentrations in maternal plasma from the end of the first trimester (12). In contrast, the ovine placenta does not seem to contribute to circulating fetal CNP concentrations, which are much lower than maternal concentrations (12). Nonetheless, as in the human fetus (13), fetal CNP synthesis is likely to be high, as shown by the very high concentrations of NTproCNP in fetal plasma. Fetal CNP forms are clearly regulated independently of maternal concentrations (10), but the sites of synthesis and the source of NTproCNP in the fetal circulation remain to be determined.A striking feature of the pattern of maternal plasma CNP forms in healthy pregnant ewes is the sudden decline in both NTproCNP and CNP within the last week of pregnancy (12)-a phase of rapidly increasing fetal cortisol production (14). Mindful of the inhibitory effects o...

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Section: Discussionmentioning

confidence: 72%

“…Peptide standards were made from synthetic human proCNP (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), taking into account the purity data supplied (Chiron Technologies, Victoria, Australia).Within-and between-assay coefficients of variation were 4.9 and 6.4%, respectively, at 22 pmol/L.…”

Section: Animalsmentioning

confidence: 99%

Effect of Cortisol on C-Type Natriuretic Peptide in Ovine Pregnancy: Differential Responses in Fetal and Placental Tissues

et al. 2010

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“…The effect of MCE on UCP2 in the lung is the opposite of the response of the brown adipose tissuespecific UCP1, which has been shown to be downregulated (Pearce et al 2005). Both thyroid hormones and glucocorticoids are known to have critical roles in promoting mitochondrial protein abundance in preparation for life after birth (Symonds 1995, Fowden et al 1998 and are, therefore, likely to be important in mediating the observed adaptations in UCP2 (Gnanalingham et al 2005d). Indeed, potential glucocorticoid and thyroid response elements have been identified in the promoter region of human UCP2 (Tu et al 1999).…”

Section: The Lungmentioning

confidence: 99%

Different effects of maternal parity, cold exposure and nutrient restriction in late pregnancy on the abundance of mitochondrial proteins in the kidney, liver and lung of postnatal sheep

Yakubu¹,

Mostyn²,

Wilson³

et al. 2007

Reproduction

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Adaptation to the extrauterine environment at birth relies upon the onset of postnatal function and increased metabolism in the lungs, liver and kidney, mediated partly by activation of mitochondrial proteins such as the voltage-dependent anion channel (VDAC), cytochrome c and, in the lung only, uncoupling protein (UCP)2. The magnitude of adaptation is dependent on the maternal metabolic and endocrine environment. We, therefore, examined the influence of maternal cold exposure (MCE) induced by winter shearing of pregnant sheep in conjunction with nutrient restriction (NR; 50% reduction in maternal food intake from 110 days gestation up to term). The effect of parity was also examined, as the offspring of nulliparous mothers are growth restricted compared with multiparous offspring. All sheep were twin bearing. One twin was sampled after birth and its sibling at 30 days. In the lung, both MCE and maternal nulliparity enhanced UCP2 abundance. However, whilst VDAC abundance was decreased in both the offspring of nulliparous mothers and by NR, it was transiently raised by MCE. Kidney VDAC abundance was reduced by MCE and nulliparity, adaptations only influenced by NR in multiparous mothers. Cytochrome c abundance was raised by MCE and by NR in multiparous controls and raised in offspring of nulliparous mothers. Liver VDAC and cytochrome c abundance were transiently reduced by MCE and persistently lower in offspring of nulliparous mothers. In conclusion, changes in the maternal metabolic environment have marked tissue-specific effects on mitochondrial protein abundance in the lungs, liver and kidney that may be important in enabling the newborn to effectively adapt to the extrauterine environment.

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“…31,32 Growth factors play a major role in the maturation of organ systems prior to birth. 17 For example, in the fetus, IGFs, synthesized by the placenta and fetal liver, 33 mediate growth 34 under the regulation of glucose and insulin. 35 The ontogenies of a number of genes that have a critical role in regulating both liver growth and development in utero, as well as postnatal growth and endocrine sensitivity, 36,37 have recently been determined in the sheep.…”

Section: Liver Regeneration and Hepatic Growth Control Mechanismsmentioning

confidence: 99%

“…15 Further markers of metabolic development include glucogenic proteins: Phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase). The fetus does not produce glucose until the prepartum cortisol surge in late gestation, 16,17 relying prior to that on placental uptake of maternal glucose into the fetal circulation. Coincident with the late gestational prepartum cortisol surge, there is a corresponding increase in hepatic PEPCK and G-6-Pase activity17 and a three-to-four-fold increase in glycogen content, which provides the major source of glucose for the newborn infant.…”

Section: Introductionmentioning

confidence: 99%

Early developmental influences on hepatic organogenesis

2008

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The liver is the largest of the body's organs, with the greatest number of functions, playing a central role in coordinating metabolic homeostasis, nutrient processing and detoxification. The fetal liver forms during early gestation in response to a sequential array of distinct biological events, regulated by intrinsically programmed mechanisms and extracellular signals which instruct hepatic cells to either proliferate, differentiate or undergo apoptosis. A vast number of genes are involved in the initiation and control of liver development, many of which are sensitive to nutritional and hormonal regulation in utero. Moreover, liver mass is influenced by the gestational environment. Therefore, during periods of hepatic cell proliferation and differentiation, the developing fetal liver is sensitive to damage from both internal and external sources including teratogens, infection and nutritional deficiencies. For example, fetuses exposed to decreased materno-fetal nutrition during late gestation have a reduced liver mass, and/or perturbed liver function, which includes increased plasma LDL cholesterol and fibrinogen concentrations. These occur in conjunction with other risk factors present in the early stages of cardiovascular disease i.e. decreased glucose tolerance and insulin insensitivity in later life. Taken together, these findings suggest that liver mass, and later function, are essentially set in utero during fetal development-a process that is ultimately regulated by the intrauterine environment.

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Glucocorticoids and the preparation for life after birth: are there long-term consequences of the life insurance?

Cited by 422 publications

References 82 publications

Effect of Cortisol on C-Type Natriuretic Peptide in Ovine Pregnancy: Differential Responses in Fetal and Placental Tissues

Effect of Cortisol on C-Type Natriuretic Peptide in Ovine Pregnancy: Differential Responses in Fetal and Placental Tissues

Different effects of maternal parity, cold exposure and nutrient restriction in late pregnancy on the abundance of mitochondrial proteins in the kidney, liver and lung of postnatal sheep

Early developmental influences on hepatic organogenesis

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