Antenatal dexamethasone: effect on ovine placental 11beta-hydroxysteroid dehydrogenase type 2 expression and fetal growth.
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.
Kerzner
Leslie S
LS
Brown University School of Medicine, Department of Pediatrics, Women and Infants' Hospital of Rhode Island, Providence 02905, USA.
Stonestreet
Barbara S
BS
Wu
Ke-Ying
KY
Sadowska
Grazyna
G
Malee
Maureen P
MP
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D005865:Gestational Age; D006854:Hydrocortisone / Q000097:blood; D006913:Hydroxysteroid Dehydrogenases / Q000096:biosynthesis* / Q000235:genetics; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects; D010920:Placenta / Q000187:drug effects / Q000201:enzymology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep
D012333:RNA, Messenger; D003907:Dexamethasone; D006913:Hydroxysteroid Dehydrogenases; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D006854:Hydrocortisone