MATERNAL CORTICOSTEROIDS AND FETAL HOMEOSTASIS

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During pregnancy in sheep and in human beings maternal plasma cortisol concentrations are increased above the level in the nonpregnant state. The goal of this proposal is to test the hypothesis that the elevated cortisol concentrations of pregnancy are essential for maternal and fetal homeostasis. Maternal cortisol concentrations are the primary source of fetal cortisol for much of gestation, therefore, increased maternal cortisol may be necessary for fetal, as well as maternal, fluid homeostasis before maturation of the fetal adrenal cortex. Increased maternal cortisol concentrations may also indirectly contribute to fetal homeostasis by control of maternal fluid balance and uterine blood flow. The proposed studies will compare fluid balance and the hormones related to volume homeostasis in the ewe and fetus in six different experimental groups: normal pregnant ewes, and pregnant adrenalectomized ewes given replacement of cortisol to very low plasma concentrations or to normal concentrations for a pregnant ewe, or with replacement of cortisol to normal levels but aldosterone to lower than than normal levels; we will also include two groups in which cortisol or aldosterone are replaced to normal levels in the fetus, despite decreased maternal cortisol or aldosterone levels. We hypothesize that decreased maternal cortisol will result in activation of vasopressin and the renin-angiotensin system in the mother and decreased transplacental fluid flux and/or decreased uterine blood flow, and that this results in chronic hypoxia and growth retardation of the fetus. We predict that this pattern will be different than that observed with reduction of plasma aldosterone. We predict that this pattern will be different than that observed with reduction of plasma aldosterone. We predict that the reduction of maternal cortisol and/or water delivery to the fetus will result in reduced fetal urine and lung liquid production rates as compensatory mechanism to maintain fetal pressure and blood volume. Basal values for fetal and maternal blood volume and pressure, plasma electrolyte and plasma protein concentrations and for fetal and maternal vasopressin, renin activity and atrial naturietic peptide will be measured at 110-125 days of gestation, before the fetal adrenal secretes appreciable quantities of cortisol. Fetal and maternal blood flow distribution and fetal urine flow and lung liquid production will also be measured to test the hypothesis that the fetus will attempt to regulate its blood pressure and volume through fluid conservation. The results of these studies will indicate whether volume homeostasis in the fetus depends on maternal cortisol concentration.