Low-dose cortisol infusion increases plasma corticosteroid-binding globulin (CBG) and the amount of hepatic CBG mRNA in fetal sheep on day 100 of gestation

Berdusco, E. T. M.; Milne, W. K.; Challis, John

doi:10.1677/joe.0.1400425

Cited by 25 publications

(9 citation statements)

References 18 publications

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“…It has been suggested previously that an increase in fetal plasma CBG late in gestation maintains low concentrations of circulating cortisol and therefore maintains low negative feedback on the pituitary and the hypothalamus (Ballard et al 1982, Berdusco et al 1994. Glucocorticoids have been shown to increase plasma CBC and hepatic CBG mRNA in fetal sheep (Berdusco et al 1994).…”

Section: Discussionmentioning

confidence: 97%

Effects of repeated maternal betamethasone administration on growth and hypothalamic-pituitary-adrenal function of the ovine fetus at term

Sloboda

Newnham²,

Challis³

2000

Journal of Endocrinology

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Synthetic glucocorticoids have become an important clinical tool with which to advance fetal lung maturation in women at risk of early preterm birth, and this has succeeded in reducing neonatal mortality and morbidity from respiratory distress syndrome. Although previous studies have shown that glucocorticoids have deleterious consequences on fetal development, there is little information regarding the effects of clinically relevant repeated maternal doses of glucocorticoids on fetal growth and hypothalamic-pituitary-adrenal (HPA) function. We hypothesised that repeated prenatal exposure to increased concentrations of glucocorticoids would alter fetal growth and HPA axis development. Pregnant ewes were injected with betamethasone (0·5 mg/kg) or vehicle at 104, 111 and 118 days of gestation (term 150 days). Animals were sacrificed at 125 and 146 days of gestation, at which time fetal weights were recorded. Maternal and fetal blood samples were gathered and fetal tissue collected. Maternal oestradiol concentrations were significantly greater than those in controls at 125 days of gestation, but were not different at 146 days. Maternal plasma progesterone concentrations were similar between groups at both 125 and 146 days of gestation. Weight at birth was significantly reduced by 23% at 125 days and 19% at 146 days of gestation (P<0·05) after exposure to glucocorticoid. Cord plasma ACTH concentrations were not significantly different between groups at day 125, but were significantly increased in day 146 fetuses of ewes that had received betamethasone (P<0·05). Cord plasma cortisol concentrations followed the same trend, although differences were not statistically significant. Cord plasma corticosteroid binding capacity (CBC) was significantly increased at 125 days of gestation in fetuses of betamethasone-treated animals (P<0·05), but not at 146 days of gestation. To examine the mechanisms regulating the increase in cord plasma ACTH of 146-day fetuses, we used in situ hybridisation to determine the distribution and levels of mRNA encoding key pituitary and hypothalamic neuropeptides of the HPA axis. In pituitaries of 146-day fetuses, there were no significant differences in the regional pattern of distribution or amounts of pro-opiomelanocortin (POMC) mRNA between betamethasone-treated animals and controls, in either the pars intermedia or the inferior and superior regions of the pars distalis. Neither prohormone convertase (PC)-1 nor PC-2 mRNA levels in pituitaries of 146-day fetuses were significantly different between treatment groups. After maternal betamethasone, immunoreactive ACTH peptide content in the fetal pars distalis was not different but glucocorticoid receptor (GR) mRNA levels in the pars distalis were increased significantly (P<0·05). No significant difference in distribution pattern or concentrations of corticotrophin-releasing hormone (CRH) mRNA, GR mRNA, oxytocin mRNA and pre-proenkephalin mRNA were found in hypothalami from fetuses at 146 days of gestation after betamethasone treatment. We...

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Section: Discussionmentioning

confidence: 97%

Effects of repeated maternal betamethasone administration on growth and hypothalamic-pituitary-adrenal function of the ovine fetus at term

Sloboda

Newnham²,

Challis³

2000

Journal of Endocrinology

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“…molecular cloning of a part of the promoter of the human CBG gene [30] failed to evidence consensus sites for steroid receptors. However, physiological changes in plasma cortisol due to infusion of this hormone increased significantly CBG mRNA in the fetal sheep liv er and the corresponding corticosteroid-binding capacity in the plasma [31]. This was even prior to the activation by glucocorticoids of the fetal hypothalamic-pituitaryadrenal axis, that play a crucial role for delivery in this species.…”

Section: Regulation Factorsmentioning

confidence: 93%

Regulation Factors of Corticosteroid-Binding Globulin; Lesson from Ontogenesis

Séralini¹

1996

Horm Res

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This short review summarizes recent data on corticosteroid-binding globulin (CBG), especially enlightening results on regulation factors of CBG gene expression during ontogenesis. The role of CBG as a specific steroid carrier, a structurally conserved glycoprotein of 50-60 kD in vertebrate species, is well documented, but this knowledge has often been limited to the young or adult life since CBG levels are low in the neonate. However, CBG and CBG mRNA have been recently detected, sometimes in relatively high amounts, in various fetal tissues of mammals including liver, lung, pancreas, adrenal and kidney. CBG can thus participate in glucocorticoid-inducible events crucial for maturation. Moreover, its original molecular cloning, followed by its chromosomal localization, has shed a new light on the CBG role, as a member of the serine protease inhibitors and substrates (SERPINS) superfamily. This evidenced a special and unexpected way of steroid hormones delivery to their sites of action. Additionally, two classes of CBG receptors have been characterized, and an adenylate cyclase activity has been measured when the CBG-glucocorticoid complex binds to cell membranes.

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“…The major site of CBG production is the liver, where CBG mRNA levels increase with advancing gestational age (110). Cortisol increases hepatic CBG mRNA, thus providing a mechanism whereby cortisol itself may maintain low free cortisol concentrations in the fetal circulation (121,122). Using pituitary cells in culture is has been shown that CBG attenuates the negative feedback effects of cortisol on ACTH secretion, thus indicating a physio¬ logical role for systemic CBG in modulating cortisol feedback efficacy at the level of the pituitary gland (119).…”

Section: Hypothalamic Drivementioning

confidence: 99%

“…Effect of intravenous administration of saline (O) or N-methyl-D-aspartate (NMDA) (·) on ACTH secretion in catheterized fetal sheep between days[110][111][112][113][114][115] (N = 5) [120][121][122][123][124][125]. (N = 5) and[135][136][137][138][139][140] (N = 8).…”

mentioning

confidence: 99%

Neuroendocrine regulation of pituitary–adrenal function during fetal life

Hagan²,

Howe³

1996

European Journal of Endocrinology

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During late gestation there is a rise in the concentration of corticosteroids in the fetal circulation that is essential for the coordinated maturation of many fetal organ systems and is a key component in the endocrine pathway leading to the onset of birth. Fetal plasma concentrations of adrenocorticotrophin (ACTH) increase during late gestation and this rise precedes the increase in plasma corticosteroids. Paradoxically, ACTH and cortisol concentrations increase concomitantly even though cortisol would normally be expected to exert negative feedback effects to inhibit pituitary ACTH secretion. Elucidating the neuroendocrine signals that cause the increase in fetal ACTH, despite the elevated concentrations of cortisol at this time, will therefore provide vital clues as to the trigger for fetal organ maturation and birth. This article describes the normal ontogeny of the hypothalamo-pituitary-adrenal axis, discusses the neuroendocrine signals that trigger the increase in fetal ACTH secretion and provides potential explanations for the concomitant rise in ACTH and cortisol.

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Low-dose cortisol infusion increases plasma corticosteroid-binding globulin (CBG) and the amount of hepatic CBG mRNA in fetal sheep on day 100 of gestation

Cited by 25 publications

References 18 publications

Effects of repeated maternal betamethasone administration on growth and hypothalamic-pituitary-adrenal function of the ovine fetus at term

Effects of repeated maternal betamethasone administration on growth and hypothalamic-pituitary-adrenal function of the ovine fetus at term

Regulation Factors of Corticosteroid-Binding Globulin; Lesson from Ontogenesis

Neuroendocrine regulation of pituitary–adrenal function during fetal life

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