Antenatal dexamethasone: effect on ovine placental 11beta-hydroxysteroid dehydrogenase type 2 expression and fetal growth

Pediatr Res. 2002 Nov;52(5):706-12. doi: 10.1203/00006450-200211000-00016.

Abstract

Antenatal glucocorticoids are routinely given to women at risk for preterm delivery. The fetus is protected from excessive glucocorticoids by the placental enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD-2), which catalyzes the conversion of cortisol to its biologically inactive metabolite, cortisone. We examined the effects of antenatal dexamethasone on the expression of placental 11beta-HSD-2 in fetal sheep. Ewes were randomized to receive repeated or single courses of dexamethasone or placebo beginning at 76-78 or 104-106 d of gestation, respectively. In the single course group, the ewes received dexamethasone (6 mg, n = 7) or placebo (n = 6) as four intramuscular injections over 48 h up to 18 h before placental harvest. In the repeated course group, the ewes received the same treatment (dexamethasone, n = 10, or placebo, n = 9) once a week for 5 consecutive weeks starting at 76-78 d of gestation. Placental harvest occurred at 106-108 d of gestation in the four groups. By semi-quantitative RT-PCR, we found that placental 11beta-HSD-2 expression was lower in the fetuses of ewes exposed to a single course of dexamethasone than placebo (p < 0.05). Placental 11beta-HSD-2 expression did not differ significantly between fetuses of ewes treated with repeated courses of dexamethasone compared with placebo, or a single course of dexamethasone. Fetuses of dexamethasone treated ewes weighed less than those of placebo treated ewes (ANOVA, main effects for dexamethasone versus placebo treatment: F = 14.5, p = 0.007). Fetuses of ewes exposed to repeated courses of dexamethasone weighed less than those of ewes exposed to placebo or a single course of dexamethasone (p < 0.05). We conclude that maternal antenatal dexamethasone treatment reduces placental 11beta-HSD-2 expression and fetal weight at mid-gestation in the ovine pregnancy.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 2
  • Animals
  • Birth Weight / drug effects
  • Dexamethasone / administration & dosage
  • Dexamethasone / pharmacology*
  • Drug Administration Schedule
  • Embryonic and Fetal Development / drug effects*
  • Enzyme Induction / drug effects
  • Female
  • Fetus / drug effects*
  • Gene Expression Regulation, Developmental / drug effects*
  • Gestational Age
  • Hydrocortisone / blood
  • Hydroxysteroid Dehydrogenases / biosynthesis*
  • Hydroxysteroid Dehydrogenases / genetics
  • Hypothalamo-Hypophyseal System / drug effects
  • Pituitary-Adrenal System / drug effects
  • Placenta / drug effects
  • Placenta / enzymology*
  • Pregnancy
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sheep

Substances

  • RNA, Messenger
  • Dexamethasone
  • Hydroxysteroid Dehydrogenases
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2
  • Hydrocortisone