Adrenocortical activity and placental glucocorticoid metabolism in the diabetic rat

ISSN： 1473-0774

Source： Prenatal and Neonatal Medicine, Vol.6, Iss.1, 2001-02, pp. : 54-64

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Abstract

Objective: The purpose of this study was to examine the effect of streptozotocin-induced diabetes on placental expression of 11-hydroxysteroid dehydrogenase and the glucocorticoid receptor, adrenocortical gene expression, plasma corticosteroids and their regulation by the hypothalamic-pituitary axis and renin-angiotensin system in rats. Study design: Non-pregnant and pregnant Sprague-Dawley rats, control and diabetic, were placed on routine, dexamethasone and low-salt diets. The expression of placental 11-hydroxysteroid dehydrogenase and the glucocorticoid receptor was determined by reverse transcriptase-polymerase chain reactions. Expression of adrenal 3-hydroxysteroid dehydrogenase, P450 sidechain cleavage (P450scc), P450 11-hydroxylase and P450 aldosterone synthase was determined by RNase protection assays. Levels of corticosterone, aldosterone and insulin were measured by radioimmunoassay, and glucose concentrations by the glucose oxidase method. Results Diabetics were hyperglycemic and insulinopenic, and corticosterone levels paralleled levels of glycemia in non-pregnant and pregnant diabetic groups. Placental expression of 11-hydroxysteroid dehydrogenase was increased in diabetic gestations, whereas glucocorticoid receptor expression was similar in control and diabetic groups. Pregnancy was accompanied by increased aldosterone levels regardless of diabetic status. Dexamethasone treatment was accompanied by decreases in aldosterone and corticosterone, whereas the low-salt diet increased aldosterone. Decreased adrenal expression of P450scc and increased 3-hydroxysteroid dehydrogenase accompanied pregnancy, whereas 3-hydroxysteroid dehydrogenase expression was decreased in diabetes. P450c11 hydroxylase adrenal expression was decreased in pregnancy, and that of P450c11 aldosterone synthase was decreased with diabetes. Conclusion: Elevated glucocorticoid levels accompany hyperglycemia. Diabetes is associated with increased expression of placental 11-hydroxysteroid dehydrogenase, presumably protecting the fetus from glucocorticoid excess. Anticipated changes in plasma corticosteroids accompany manipulations of the hypothalamic-pituitary axis and renin-angiotensin system in the pregnant and diabetic models. Diabetes and pregnancy have differential effects upon adrenocortical gene expression, which are not reflected in circulating corticosteroid levels.