Dexamethasone and betamethasone administration during pregnancy affects expression and function of 11 beta-hydroxysteroid dehydrogenase type 2 in the rat placenta.
Placental 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) is the key enzyme which protects the fetus from overexposure to glucocorticoids (GCs) by their oxidation into inactive derivates. Several recent studies suggest that 11 beta-HSD2 expression is subjected to regulation by antenatal steroid therapy. In our study we investigated the effect of two commonly used synthetic steroids, dexamethasone (DXM) and betamethasone (BTM), on the expression and function of 11 beta-HSD2 in the rat placenta. Pregnant rats were pretreated with low (0.2mg/kg) or high (5mg/kg and 11.5mg/kg for DXM and BTM, respectively) i.m. doses of GCs. 11 beta-HSD2 expression was investigated using real-time RT-PCR and Western blotting; conversion capacity of 11 beta-HSD2 was assessed by dual perfusion of the rat placenta. Significant increase in placental 11 beta-HSD2 mRNA expression was found in rats treated with DXM, however, this alteration was not observed on protein level. BTM had no effect on either mRNA or protein levels of 11 beta-HSD2. Functional studies revealed that both GCs significantly reduced the metabolism of corticosterone by the placenta. Our data indicate that placental barrier function mediated by 11 beta-HSD2 might be considerably impaired by the antenatal therapy with DXM and BTM. In addition, the discrepancy between expressional and functional studies suggests that sole analysis of expressional changes of 11 beta-HSD2 at mRNA and/or protein levels cannot convincingly predict the role of GC treatment on 11 beta-HSD2 function in the placental barrier.
Vackova
Zuzana
Z
Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic.
Vagnerova
Karla
K
Libra
Antonin
A
Miksik
Ivan
I
Pacha
Jiri
J
Staud
Frantisek
F
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001623:Betamethasone / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D001724:Birth Weight / Q000187:drug effects; D015153:Blotting, Western; D003907:Dexamethasone / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D007273:Injections, Intramuscular; D010477:Perfusion; D010920:Placenta / Q000187:drug effects* / Q000201:enzymology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005938:Glucocorticoids; D012333:RNA, Messenger; D003907:Dexamethasone; D001623:Betamethasone; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2