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Research Data supporting: "Prenatal cortisol exposure impairs adrenal function but not glucose metabolism in adult sheep"


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The excel spread sheet contains the data presented in the publication that investigated the effects of prenatal cortisol infusion on pituitary-adrenal function and glucose-insulin dynamics in adult sheep compared to the effects of prenatal saline infusion. The spread sheet contains tabs for tabulated data of the absolute values for (1) postnatal biometry, (2) adult adrenal morphology, (3) fetal cortisol concentrations during cortisol and saline infusion before birth, (3) cortisol concentrations for the cortisol and saline infused fetuses during infusion, (4) basal and steady state blood glucose and plasma insulin concentration, steady state glucose infusion rate , insulin sensitivity and insulin clearance rates during the hyperinsulinaemic-euglucaemic clamps in the adult sheep infused with cortisol or saline prenatally, (5) blood glucose and plasma insulin concentrations, their increments from basal values, the areas under their response curves, relative insulin secretion and half time for glucose disappearance during the glucose tolerance test in the adult sheep infused with cortisol or saline prenatally (6) blood glucose concentrations and its decrement together with the plasma concentrations of cortisol and ACTH and their increments from basal values in response to insulin administration in the adult sheep infused with cortisol or saline prenatally and (7) Plasma concentrations of cortisol, its increment from basal values and the area under the response curve in the adult sheep infused with cortisol or saline prenatally. Abbreviations are given on each tab. See main manuscript for more details.

Abstract for publication:

Adverse environmental conditions before birth are known to program adult metabolic and endocrine phenotype in several species. However, whether increments in fetal cortisol concentrations of the magnitude commonly seen in these conditions can cause developmental programming remains unknown. Thus, this study investigated the outcome of physiological increases in fetal cortisol concentrations on glucose-insulin dynamics and pituitary-adrenal function in adult sheep. Compared to saline treatment, intravenous fetal cortisol infusion for 5 days in late gestation did not affect birthweight but increased lamb body weight at 1-2 weeks after birth. Adult glucose dynamics, insulin sensitivity and insulin secretion were unaffected by prenatal cortisol overexposure, assessed by glucose tolerance tests, hyperinsulinaemic-euglycaemic clamps and acute insulin administration. In contrast, prenatal cortisol infusion induced adrenal hypo-responsiveness in adulthood with significantly reduced cortisol responses to insulin-induced hypoglycaemia and exogenous adrenocorticotropic hormone (ACTH) administration relative to saline treatment. The area of adrenal cortex expressed as a percentage of the total cross-sectional area of the adult adrenal gland was also lower after prenatal cortisol than saline infusion. In adulthood, basal circulating ACTH but not cortisol concentrations were significantly higher in the cortisol than saline treated group. The results show that cortisol overexposure before birth programs pituitary-adrenal development with consequences for adult stress responses. Physiological variations in cortisol concentrations before birth may, therefore, have an important role in determining adult phenotypical diversity and adaptability to environmental challenges.

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Excel spread sheet

Keywords

Cortisol, Developmental programming, Pituitary-adrenal function and glucose-nsulin dynamics

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Biotechnology and Biological Sciences Research Council (BB/P019048/1)
Biotechnology and Biological Science Research Council
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