Adrenocortical activity and placental glucocorticoid metabolism in the diabetic rat

Objective The purpose of this study was to examine the effect of streptozot ocin-induced diabetes on placental expression of 11 beta -hydroxysteroid de hydrogenase 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 dia betic, were placed on routine, dexamethasone and low-salt diets. The expres sion of placental 11 beta -hydroxysteroid dehydrogenase glucocorticoid rece ptor was determined by reverse transcriptase-polymerase chain reactions. Ex pression of adrenal 3 beta -hydroxysteroid dehydrogenase. P450 sidechain cl eavage (P450scc), P450 1-hydroxylase and P450 aldosterone synthase was dete rmined by RNase protection assays. Levels of corticosterone, aldosterone an d 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 beta -hydroxysteroid dehydrogenase was i ncreased in diabetic gestations, whereas glucocorticoid receptor expression was similar in control and diabetic groups. Pregnancy was accompanied by i ncreased aldosterone levels regardless of diabetic status. Dexamethasone tr eatment was accompanied by decreases in aldosterone and corticosterone, whe reas the low-salt diet increased aldosterone, Decreased adrenal expression of P450scc and increased 3 beta -hydroxysteroid dehydrogenase accompanied p regnancy, whereas 3 beta -hydroxysteroid dehydrogenase expression was decre ased in diabetes. P450c11 hydroxylase adrenal expression was decreased in p regnancy, and that of P450c11 aldosterone synthase was decreased with diabe tes. Conclusion Elevated glucocorticoid levels accompany hyperglycemia. Diabetes is associated with increased expression of placental 11 beta -hydroxystero id dehydrogenase, presumably protecting the fetus from glucocorticoid exces s. Anticipated changes in plasma corticosteroids accompany manipulations of the hypothalamic-pituitary axis and renin-angiotensin system in the pregna nt and diabetic models. Diabetes and pregnancy have differential effects up on adrenocortical gene expression, which are not reflected in circulating c orticosteroid levels.