LOW-DOSE CORTISOL INFUSION INCREASES PLASMA CORTICOSTEROID-BINDING GLOBULIN (CBG) AND THE AMOUNT OF HEPATIC CBG MESSENGER-RNA IN FETAL SHEEP ON DAY-100 OF GESTATION

Synthetic glucocorticoids stimulate the production of corticosteroid-b inding globulin (CBG) by the liver of the sheep fetus near term (day 1 45). We have examined whether physiological changes in plasma cortisol alter plasma CBG concentrations, patterns of glycosylation and the am ount of hepatic CBG mRNA at earlier times during pregnancy (day 100), prior to the activation of fetal hypothalamic-pituitary-adrenal functi on. Cortisol was infused into chronically catheterized sheep fetuses i n amounts that raised the plasma cortisol concentrationby about 15 nmo l/l. This treatment resulted in a significant increase in the plasma c orticosteroid-binding capacity and in the amount of CBG mRNA in the fe tal liver, but did not alter the proportion of CBG retained using Conc anavalinA chromatography. We conclude that the CBG gene in the liver o f fetal sheep responds to physiological changes in plasma concentratio n of cortisol and we speculate that the rise in plasma CBG concentrati on is important in diminishing the negative feedback effect of circula ting cortisol on the fetal pituitary and hypothalamus.