Effects of incremental cortisol and adrenalectomy on plasma corticosteroid binding capacity in fetal sheep

Jeffray, T; Berdusco, E. T. M.; Wallace, Megan Jane; Fowden, AL; Challis, J. R. G.

doi:10.1139/y95-216

Cited by 10 publications

(5 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CBG is primarily produced in the fetal liver (Ballard et al 1982, Berdusco et al 1993) and regulates local and circulating levels of cortisol, resulting in an overall decrease in bioactive glucocorticoids (Berdusco et al 1993. Many studies have reported that glucocorticoids regulate both CBG expression levels and activity (Challis et al 1985, Berdusco et al 1993, Jeffray et al 1995. It has been demonstrated previously that increasing levels of plasma cortisol correlate positively with the activity of key hepatic enzymes involved in gluconeogenesis, such as PEPCK and glucose-6-phosphatase (Fowden et al 1990(Fowden et al , 1993.…”

Section: Discussionmentioning

confidence: 97%

Repeated maternal glucocorticoid administration and the developing liver in fetal sheep

Sloboda¹,

Newnham²,

Challis³

2002

Journal of Endocrinology

View full text Add to dashboard Cite

Prenatal glucocorticoid exposure has been associated with a reduction in birth weight and postnatal alterations in glucose homeostasis and hypothalamic-pituitary-adrenal (HPA) axis function. The mechanisms underlying these responses are unknown, although changes in fetal hepatic development may play an important role. The fetal liver produces key regulators of fuel metabolism and of the developing HPA axis that are altered by glucocorticoids. The local availability of glucocorticoids is regulated, in part, by corticosteroid-binding protein (CBG), glucocorticoid receptors (GR) and by the enzyme 11 -hydroxysteroid dehydrogenase (11 HSD), but the effects of maternal glucocorticoid administration on the expression of these genes in the fetal liver are unknown. 11 HSD1 is the predominant form of this enzyme present in the liver and is responsible for the conversion of cortisone to cortisol. To determine if prenatal glucocorticoid exposure alters fetal hepatic regulation of CBG, 11 HSD1 and GRs, we treated pregnant ewes with betamethasone (0·5 mg/kg) intramuscularly at 104, 111 and 118 days of gestation (term 150 days). Animals were killed at 125 or 146 days of gestation. Maternal betamethasone administration did not alter mean cord plasma glucose but significantly decreased cord plasma insulin levels (P<0·05) at 125 days of gestation. At 146 days of gestation, cord plasma glucose levels were significantly increased without alterations in insulin levels following maternal betamethasone treatment (P<0·05). Maternal betamethasone administration resulted in a significant increase in fetal hepatic 11 HSD1 mRNA and protein levels at 125 days of gestation (P<0·05). CBG mRNA levels were significantly elevated over control at 125 days although levels of CBG protein were not significantly different. GR protein levels were not statistically different at either 125 or 146 days of gestation following glucocorticoid administration. These data suggest that prenatal betamethasone exposure in the ovine fetus results in alterations in cord glucose and insulin levels as well as alterations in hepatic 11 HSD1 mRNA and protein expression. These changes in 11 HSD1 increase the potential to generate local cortisol from circulating cortisone. We speculate that this could affect expression of glucocorticoid-dependent hepatic enzymes involved with the regulation of glucose production and HPA responsiveness.

show abstract

Section: Discussionmentioning

confidence: 97%

Repeated maternal glucocorticoid administration and the developing liver in fetal sheep

Sloboda¹,

Newnham²,

Challis³

2002

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Plasma cortisol concentrations were quantified by RIA after extraction with diethyl ether. The antibody characteristics have been described previously (Jeffray et al 1995). The intra-assay coefficient of variation was 6%, the inter-assay 15%.…”

Section: Measurement Of Plasma Acth and Cortisolmentioning

confidence: 99%

The effect of prenatal betamethasone administration on postnatal ovine hypothalamic-pituitary-adrenal function

Sloboda

Moss

Gurrin

et al. 2002

Journal of Endocrinology

145

129

View full text Add to dashboard Cite

Prenatal exposure to glucocorticoids is associated with alterations in fetal growth and endocrine function. However, few studies have examined the effects of clinically relevant doses of glucocorticoids on postnatal hypothalamic-pituitary-adrenal (HPA) function. To determine the effects of maternal or fetal betamethasone administration (0·5 mg/kg maternal or estimated fetal weight) on postnatal HPA function at 6 months and 1 year postnatal age, pregnant ewes were randomized into the following treatment groups: no treatment (n=6); maternal saline (n=6); single maternal betamethasone (M1) (n=6); repeated maternal betamethasone (M4) (n=6); fetal saline (n=5); single fetal betamethasone (n=6) and repeated fetal betamethasone (F4) (n=6). Single injections were given at 104 days of gestation and repeated injections at 104, 111, 118 and 125 days. Lambs were born spontaneously and the ACTH and cortisol responses to i.v. corticotropinreleasing hormone (CRH) (0·5 µg/kg) plus arginine vasopressin (AVP) (0·1 µg/kg) were measured at 6 months and 1 year postnatally. At 6 months postnatal age, neither maternal nor fetal prenatal betamethasone administration altered significantly the ACTH and cortisol responses to CRH+AVP. However, in animals at 1 year postnatal age, a previous single injection of betamethasone to the mother (M1) resulted in significantly elevated basal and stimulated cortisol levels (P<0·05), without significant change in the ACTH response. In contrast, betamethasone administration to the fetus resulted in significantly attenuated ACTH responses to CRH+AVP at 1 year compared with control animals (P<0·05), but these were not associated with any significant changes in basal or stimulated cortisol levels. All control animals exhibited a significant increase in peak ACTH responses to CRH+AVP between 6 months and 1 year postnatal age (P<0·05). After prenatal betamethasone (F4, M4) the difference in peak ACTH response between animals at 6 months and 1 year postnatal age was abolished. We conclude that in sheep between 6 months and 1 year postnatal age, HPA function undergoes developmental changes that are influenced by prenatal glucocorticoid exposure. Furthermore, the effects of glucocorticoid on postnatal HPA responses may vary according to the time in gestation that the steroid was administered, and whether it was given directly into the fetal or maternal compartment.

show abstract

“…2;Jones & Rolph, 1985;Fowden et al 1993). Cortisol has also been shown to be responsible for the normal prepartum rise in corticosteroid-binding globulin synthesis in the liver and in the hepatic activity of the 5'monodeiodinase which stimulates outer-ring deiodination of thyroxine to triiodothyronine (thyroxine deiodinase; EC 3.8.1.4; Wu et al 1978;Jeffray et al 1995). The ontogenic up-regulation in receptor density for growth hormone (GH), prolactin and P-adrenoreceptors in the ovine fetal liver is also dependent on the fetal plasma cortisol surge (Li et al 1996b;Barnes, 1997;Phillips ID et al 1997).…”

mentioning

confidence: 99%

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

1998

View full text Add to dashboard Cite

Effects of incremental cortisol and adrenalectomy on plasma corticosteroid binding capacity in fetal sheep

Cited by 10 publications

References 16 publications

Repeated maternal glucocorticoid administration and the developing liver in fetal sheep

Repeated maternal glucocorticoid administration and the developing liver in fetal sheep

The effect of prenatal betamethasone administration on postnatal ovine hypothalamic-pituitary-adrenal function

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

Contact Info

Product

Resources

About