{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:21:21Z","timestamp":1784557281462,"version":"3.55.0"},"reference-count":62,"publisher":"Bioscientifica","issue":"3","license":[{"start":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T00:00:00Z","timestamp":1702857600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,12,18]]},"abstract":"<jats:p>Adverse environmental conditions before birth are known to programme adult metabolic and endocrine phenotypes 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\u2013insulin dynamics and pituitary\u2013adrenal function in adult sheep. Compared with saline treatment, intravenous fetal cortisol infusion for 5 days in late gestation did not affect birthweight but increased lamb body weight at 1\u20132 weeks after birth. Adult glucose dynamics, insulin sensitivity and insulin secretion were unaffected by prenatal cortisol overexposure, assessed by glucose tolerance tests, hyperinsulinaemic\u2013euglycaemic 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 programmes pituitary\u2013adrenal 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.<\/jats:p>","DOI":"10.1530\/joe-23-0326","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T12:39:47Z","timestamp":1702903187000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":1,"title":["Prenatal cortisol exposure impairs adrenal function but not glucose metabolism in adult sheep"],"prefix":"10.1530","volume":"260","author":[{"given":"K L","family":"Davies","sequence":"first","affiliation":[{"name":"Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Miles","sequence":"additional","affiliation":[{"name":"Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E J","family":"Camm","sequence":"additional","affiliation":[{"name":"Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, UK"},{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D J","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Barker","sequence":"additional","affiliation":[{"name":"MRC Metabolic Diseases Unit, Mouse Biochemistry Laboratory, Cambridge Biomedical Campus, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Taylor","sequence":"additional","affiliation":[{"name":"Endocrine Laboratory, Blood Sciences, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A J","family":"Forhead","sequence":"additional","affiliation":[{"name":"Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, UK"},{"name":"Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3384-4467","authenticated-orcid":true,"given":"A L","family":"Fowden","sequence":"additional","affiliation":[{"name":"Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Endocrinology","first-page":"2933","article-title":"Brief undernutrition in late-gestation sheep programs the hypothalamic-pituitary-adrenal axis in adult offspring","volume":"144","author":"Bloomfield","year":"2003","unstructured":"Bloomfield FHOliver MHGiannoulias DGluckman PDHarding JE & Challis JRG2003Brief undernutrition in late-gestation sheep programs the hypothalamic-pituitary-adrenal axis in adult offspring. 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