Adrenocortical imprint in the fetus of a diabetic gestation.
Offspring of diabetics are at increased risk for diabetes as adults. As corticosteroids are intimately involved in glucose homeostasis, we investigated aspects of corticosteroid activity in the late gestation fetuses of control, moderately diabetic and insulin-controlled streptozotocin-induced diabetic rats. We found that moderate maternal diabetes had no effect upon litter size or fetal body weight. Uncontrolled maternal diabetes was accompanied by fetal hyperglycemia, hyperinsulinemia and elevated aldosterone. Maternal 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 P450c11beta mRNA increased, and returned to that of the control gestation upon insulin treatment. 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 expression of a fetal adrenocortical imprint, manifested as a greater abundance of P450c11beta mRNA. Although not accompanied by elevated corticosterone in the fetus, this imprint could ultimately allow for greater potential corticosterone production in response to typical stimuli, and thus contribute to the tendency towards glucose dysregulation in these offspring of diabetic gestations.
Malee
M P
MP
Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Women and Infants' Hospital, Brown University, Providence, RI 02905, USA. mmalee@wihri.org
Wu
K Y
KY
D000302:Adrenal Cortex / Q000196:embryology*; D000311:Adrenal Glands / Q000196:embryology; D000450:Aldosterone / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003345:Corticosterone / Q000097:blood; D019405:Cytochrome P-450 CYP11B2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D005333:Fetus / Q000378:metabolism / Q000502:physiology*; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D017403:In Situ Hybridization; D007328:Insulin / Q000097:blood / Q000627:therapeutic use; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000097:blood / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012260:Ribonucleases; D013250:Steroid Hydroxylases / Q000235:genetics
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D012333:RNA, Messenger; D000450:Aldosterone; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; C120361:Cyp11b3 protein, rat; D019405:Cytochrome P-450 CYP11B2; D012260:Ribonucleases; D003345:Corticosterone