ISSN 1214-0287 (on-line), ISSN 1214-021X (printed)
J Appl Biomed
Volume 11 (2013), No 3, p 163-172
DOI 10.2478/v10136-012-0022-y

Effects of glucocorticoids on cytochrome P450 1A1 (CYP1A1) expression in isolated human placental trophoblast

Lucie Stejskalova, Radim Vrzal, Alice Rulcova, Zdenek Dvorak, Petr Pavek

Address: Petr Pavek, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic
pavek@faf.cuni.cz

Received 14th August 2012.
Revised 10th October 2012.
Published online 18th October 2012.

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SUMMARY
Antenatal glucocorticoid administration is used in cases of fetuses at risk to be born prematurely to enhance fetal pulmonary surfactant production and prevent infant respiratory distress syndrome. The CYP1A1 is the most important xenobiotic-metabolizing cytochrome P450 enzyme in the human placenta. Importantly, CYP1A1 generates reactive species and its placental activity is elevated in smoking women. CYP1A1 expression is mainly controlled by aryl hydrocarbon receptor (AHR) ligands. Glucocorticoid co-regulation of CYP1A1 has been described in various cell types but has not been systematically examined in the human placental trophoblast.
We studied the effects of the glucocorticoids dexamethasone and betamethasone on inducibility of CYP1A1 and other AHR target genes CYP1A2, CYP1B1, UGT1A1 (UDP-glucuronosyltransferase 1A1) and BCRP (Breast cancer resistance protein) by prototype AHR ligand -methylcholanthrene (3MC) in isolated human placental trophoblast culture.
We show that glucocorticoids alone had no effect on activity and protein/mRNA expression of CYP1A1 and little effect on mRNA expression of other AHR target genes. However, glucocorticoids significantly stimulated CYP1A1 mRNA, but not CYP1A2, CYP1B1, UGT1A1 and BCRP mRNAs, induction mediated by the AHR ligand. Consistently, glucocorticoids significantly augmented 7-ethoxyresorufin-O-deethylation (EROD) enzymatic activity in primary human placental trophoblast. Dexamethasone did not influence AHR and ARNT (Aryl hydrocarbon receptor nuclear translocator) mRNAs, suggesting that this phenomenon is not due to AHR or ARNT up-regulation by glucocorticoids in human trophoblast.
In conclusion, our data suggest that glucocorticoids have no effect on AHR target genes expression per se, but they may potentiate CYP1A1 induction in human term placental trophoblast.

KEY WORDS
trophoblast; aryl hydrocarbon receptor; CYP1A1; cytochrome P450; glucocorticoids; placenta

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