The effects of glucocorticoid treatment on the development and function of the hypothalmic-pituitary-adrenal axis in fetal and young sheep

    Research output: ThesisDoctoral Thesis

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    Abstract

    [Truncated abstract] Corticosteroid therapy is used routinely to mature the developing lungs of infants of mothers presenting at risk of early preterm birth, and is also used in early human pregnancy to suppress adrenal function in cases of suspected fetal congenital adrenal hyperplasia (CAH). While the beneficial effects of synthetic glucocorticoids are substantial, the long-term consequences are relatively unexplored. The Developmental Origins of Health and Disease (DOHaD) hypothesis suggests that maternal stress and glucocorticoids may contribute to programming the developmental trajectory of the fetus towards predisposition to non communicable disease in later life. In this thesis I have tested the overall hypothesis that administration of synthetic glucocorticoid during early or late pregnancy will affect placental and fetal development leading to changes in maturational responses of the fetal hypothalamic-pituitary-adrenal (HPA) axis, to altered growth parameters and to altered responses to stress stimuli in later life. Studies were conducted using time bred sheep treated with synthetic glucocorticoid in early (day 40-42) and late (days 104-118, weekly injections) pregnancy. I sought effects on HPA axis development, fetal growth and postnatal responses in newborn and 7 month-old lambs and on placental function. Maternal treatment with dexamethasone in early gestation led in late pregnancy to an exaggerated prepartum increase in fetal plasma cortisol, but not ACTH...
    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2013

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