Adrenocortical imprint in the fetus of a diabetic gestation

Offspring of diabetics are at increased risk for diabetes as adults. As cor ticosteroids are intimately involved in glucose homeostasis, we investigate d aspects of corticosteroid activity in the late gestation fetuses of contr ol, moderately diabetic and insulin-controlled streptozotocin-induced diabe tic rats. We found that moderate maternal diabetes had no effect upon litte r size or fetal body weight. Uncontrolled maternal diabetes was accompanied by fetal hyperglycemia, hyperinsulinemia and elevated aldosterone. Materna l insulin treatment normalized fetal glucose and aldosterone; fetal insulin and corticosterone levels increased. Maternal diabetes had no effect upon fetal adrenal expression of P450scc mRNA; the abundance of P450c11 beta mRN A increased, and returned to that of the control gestation upon insulin tre atment. P450c11AS mRNA was barely detectable, and decreased in the fetuses of insulin-treated diabetics. P450c11B3 mRNA was undetectable in all fetal groups. Our results implicate aspects of maternal diabetes in the expressio n of a fetal adrenocortical imprint, manifested as a greater abundance of P 450c11 beta mRNA. Although not accompanied by elevated corticosterone in th e fetus, this imprint could ultimately allow for greater potential corticos terone production in response to typical stimuli, and thus contribute to th e tendency towards glucose dysregulation in these offspring of diabetic ges tations.