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.