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1 Endocrinology Unit, Molecular Medicine Centre, School of Molecular and Clinical Medicine, Edinburgh University, Western General Hospital, Edinburgh, Scotland, United Kingdom
* To whom correspondence should be addressed. E-mail: Megan.Holmes{at}ed.ac.uk.
Glucocorticoid overexposure in utero may underlie the association between low birth weight and subsequent development of common cardiovascular and metabolic pathologies. Previously, we have shown that prenatal dexamethasone (DEX) exposure in rat reduces birth weight and programmes the hypothalamic-pituitary-axis (HPA) and fasting and postprandial hyperglycaemia in adult males and hypertension in adult males and females. This study aimed to determine (1) whether there were gender differences in prenatal DEX - programmed offspring, and (2) whether the renin-angiotensin-system (RAS) plays a role in the programming of hypertension. Rats exposed to DEX in utero (100µg.kg-1.day-1 from embryonic days 14-21), were of lower birth weight (by 12%, p <0.01) and displayed full catch-up growth within the first month of postnatal life. DEX-treated male offspring in adulthood, selectively displayed elevated plasma adrenocorticotrophin (by 221%) and corticosterone (by 188%, p <0.05), postprandial insulin:glucose ratios (by 100%, p <0.05), and hepatic expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (by 38%, p <0.05). Conversely, DEX-programmed females were hypertensive (by 11%, p <0.05) with elevated hepatic angiotensinogen mRNA expression (by 9%, p <0.05), plasma angiotensinogen (by 61%, p <0.05) and renin activity (by 88 %, p <0.05). These findings demonstrate that prenatal glucocorticoids programme adulthood cardiovascular and metabolic physiology in a gender specific pattern, and that an activated RAS may in part underlie the hypertension associated with prenatal dexamethasone programming.
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