TY - JOUR
T1 - Effects of Maternal Dexamethasone Treatment in Early Pregnancy on Pituitary-Adrenal Axis in Fetal Sheep
AU - Braun, T.
AU - Li, Shaofu
AU - Sloboda, Deborah
AU - Li, W.
AU - Audette, M.C.
AU - Moss, T.J.
AU - Matthews, S.G.
AU - Polglase, Graeme
AU - Nitsos, Ilias
AU - Newnham, John
AU - Challis, John
PY - 2009
Y1 - 2009
N2 - Fetal exposure to elevated levels of bioactive glucocorticoids early in gestation, as in suspected cases of congenital adrenal hyperplasia, may result in adverse neurological events. Fetal hypothalamic-pituitary-adrenal development and function may be involved. We investigated immediate and long-term effects of maternal dexamethasone (DEX) administration early in pregnancy on fetal growth and pituitary-adrenal activity in sheep. Pregnant ewes carrying singleton fetuses (total n = 119) were randomized to control (2 ml saline/ewe) or DEX-treated groups (im injections of 0.14 mg/kg ewe weight · 12 h) at 40–41 d gestation (dG). At 50, 100, 125, and 140 dG, fetal plasma and tissues were collected. DEX-exposed fetuses were lighter than controls at 100 dG (P <0.05) but not at any other times. Fetal plasma ACTH levels and pituitary POMC and PC-1 mRNA levels were similar between groups. Fetal plasma cortisol levels were significantly reduced after DEX exposure in both male and female fetuses at 50 dG (P <0.05), were similar at 100 and 125 dG, but were significantly higher than controls at 140 dG. At 140 dG, there was increased adrenal P450C17 and 3β-HSD mRNA in female fetuses and reduced expression of ACTH-R mRNA in males. Fetal hepatic CBG mRNA levels mimicked plasma cortisol patterns. DEX exposure reduced CBG only in males at 50 dG (P <0.05). Placental mRNA levels of 11β-HSD2 were increased after DEX in males (P <0.05). Therefore, in sheep, early DEX may alter the developmental trajectory of the fetal hypothalamic-pituitary-adrenal axis, directly increasing fetal adrenal activation but not anterior pituitary function. In females, this effect may be attributed, in part, to increased fetal adrenal steroidogenic activity.
AB - Fetal exposure to elevated levels of bioactive glucocorticoids early in gestation, as in suspected cases of congenital adrenal hyperplasia, may result in adverse neurological events. Fetal hypothalamic-pituitary-adrenal development and function may be involved. We investigated immediate and long-term effects of maternal dexamethasone (DEX) administration early in pregnancy on fetal growth and pituitary-adrenal activity in sheep. Pregnant ewes carrying singleton fetuses (total n = 119) were randomized to control (2 ml saline/ewe) or DEX-treated groups (im injections of 0.14 mg/kg ewe weight · 12 h) at 40–41 d gestation (dG). At 50, 100, 125, and 140 dG, fetal plasma and tissues were collected. DEX-exposed fetuses were lighter than controls at 100 dG (P <0.05) but not at any other times. Fetal plasma ACTH levels and pituitary POMC and PC-1 mRNA levels were similar between groups. Fetal plasma cortisol levels were significantly reduced after DEX exposure in both male and female fetuses at 50 dG (P <0.05), were similar at 100 and 125 dG, but were significantly higher than controls at 140 dG. At 140 dG, there was increased adrenal P450C17 and 3β-HSD mRNA in female fetuses and reduced expression of ACTH-R mRNA in males. Fetal hepatic CBG mRNA levels mimicked plasma cortisol patterns. DEX exposure reduced CBG only in males at 50 dG (P <0.05). Placental mRNA levels of 11β-HSD2 were increased after DEX in males (P <0.05). Therefore, in sheep, early DEX may alter the developmental trajectory of the fetal hypothalamic-pituitary-adrenal axis, directly increasing fetal adrenal activation but not anterior pituitary function. In females, this effect may be attributed, in part, to increased fetal adrenal steroidogenic activity.
U2 - 10.1210/en.2009-0086
DO - 10.1210/en.2009-0086
M3 - Article
SN - 0013-7227
VL - 150
SP - 5466
EP - 5477
JO - Endocrinology
JF - Endocrinology
IS - 12
ER -