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
REFERENCES
Avery ML, Meek CE, Audus KL. The presence of inducible cytochrome P450 types 1A1 and 1A2 in the BeWo cell line. Placenta. 24: 45-52, 2003.
[CrossRef]
[PubMed]
Ballard PL, Ballard RA. Scientific basis and therapeutic regimens for use of antenatal glucocorticoids. Am J Obstet Gynecol. 173: 254-262, 1995.
[CrossRef]
Cygalova L, Ceckova M, Pavek P, Staud F. Role of breast cancer resistance protein (Bcrp/Abcg2) in fetal protection during gestation in rat. Toxicol
Lett. 178: 176-180, 2008.
[CrossRef]
[PubMed]
Dolwick KM, Schmidt JV, Carver LA, Swanson HI, Bradfield CA. Cloning and expression of a human Ah receptor cDNA. Mol Pharmacol. 44: 911-917, 1993.
[PubMed]
Dvorak Z, Vrzal R, Pavek P, Ulrichova J. An evidence for regulatory cross-talk between aryl hydrocarbon receptor and glucocorticoid receptor in HepG2
cells. Physiol Res. 57: 427-435, 2008.
[PubMed]
Hakkola J, Pasanen M, Hukkanen J, Pelkonen O, Maenpaa J, Edwards RJ, Boobis AR, Raunio H. Expression of xenobiotic-metabolizing cytochrome P450 forms
in human full-term placenta. Biochem Pharmacol. 51: 403-411, 1996a.
[CrossRef]
Hakkola J, Raunio H, Purkunen R, Pelkonen O, Saarikoski S, Cresteil T, Pasanen M. Detection of cytochrome P450 gene expression in human placenta in
first trimester of pregnancy. Biochem Pharmacol. 52: 379-383, 1996b.
[CrossRef]
Hakkola J, Pasanen M, Pelkonen O, Hukkanen J, Evisalmi S, Anttila S, Rane A, Mantyla M, Purkunen R, Saarikoski S, Tooming M, Raunio H. Expression of
CYP1B1 in human adult and fetal tissues and differential inducibility of CYP1B1 and CYP1A1 by Ah receptor ligands in human placenta and cultured
cells. Carcinogenesis. 18: 391-397, 1997.
[CrossRef]
[PubMed]
Hallman M, Peltoniemi O, Kari MA Enhancing functional maturity before preterm birth. Neonatology. 97: 373-378, 2010.
[CrossRef]
[PubMed]
Iqbal M, Audette MC, Petropoulos S, Gibb W, Matthews SG. Placental drug transporters and their role in fetal protection. Placenta. 33: 137-142,
2012.
[CrossRef]
[PubMed]
Kliman HJ, Nestler JE, Sermasi E, Sanger JM, Strauss JF, 3rd. Purification, characterization, and in vitro differentiation of
cytotrophoblasts from human term placentae. Endocrinology. 118: 1567-1582, 1986.
[CrossRef]
[PubMed]
Lai KP, Wong MH, Wong CK. Modulation of AhR-mediated CYP1A1 mRNA and EROD activities by 17beta-estradiol and dexamethasone in TCDD-induced H411E
cells. Toxicol Sci. 78: 41-49, 2004.
[CrossRef]
[PubMed]
Lunghi L, Pavan B, Biondi C, Paolillo R, Valerio A, Vesce F, Patella A. Use of glucocorticoids in pregnancy. Curr Pharm Des. 16: 3616-3637, 2010.
[CrossRef]
[PubMed]
Marciniak B, Patro-Malysza J, Poniedzialek-Czajkowska E, Kimber-Trojnar Z, Leszczynska-Gorzelak B, Oleszczuk J. Glucocorticoids in pregnancy. Curr
Pharm Biotechnol. 12: 750-757, 2011.
[PubMed]
Meyer Zu Schwabedissen HE, Grube M, Heydrich B, Linnemann K, Fusch C, Kroemer HK, Jedlitschky G. Expression, localization, and function of MRP5
(ABCC5), a transporter for cyclic nucleotides, in human placenta and cultured human trophoblasts: effects of gestational age and cellular
differentiation. Am J Pathol. 166: 39-48, 2005.
[CrossRef]
Monostory K, Kohalmy K, Prough RA, Kobori L, Vereczkey L. The effect of synthetic glucocorticoid, dexamethasone on CYP1A1 inducibility in adult rat
and human hepatocytes. FEBS Lett. 579: 229-235, 2005.
[CrossRef]
[PubMed]
Nelson DM, Burton GJ. A technical note to improve the reporting of studies of the human placenta. Placenta. 32: 195-196, 2010.
[CrossRef]
[PubMed]
Okey AB, Giannone JV, Smart W, Wong JM, Manchester DK, Parker NB, Feeley MM, Grant DL, Gilman A. Binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin to AH
receptor in placentas from normal versus abnormal pregnancy outcomes. Chemosphere. 34: 1535-1547, 1997.
[CrossRef]
Paakki P, Kirkinen P, Helin H, Pelkonen O, Raunio H, Pasanen M. Antepartum glucocorticoid therapy suppresses human placental xenobiotic and steroid
metabolizing enzymes. Placenta. 21: 241-246, 2000.
[CrossRef]
[PubMed]
Pavek P, Cerveny L, Svecova L, Brysch M, Libra A, Vrzal R, Nachtigal P, Staud F, Ulrichova J, Fendrich Z, Dvorak Z. Examination of Glucocorticoid
receptor alpha-mediated transcriptional regulation of P-glycoprotein, CYP3A4, and CYP2C9 genes in placental trophoblast cell lines. Placenta. 28:
1004-1011, 2007.
[CrossRef]
[PubMed]
Pospechova K, Rozehnal V, Stejskalova L, Vrzal R, Pospisilova N, Jamborova G, May K, Siegmund W, Dvorak Z, Nachtigal P, Semecky V, Pavek P. Expression
and activity of vitamin D receptor in the human placenta and in choriocarcinoma BeWo and JEG-3 cell lines. Mol Cell Endocrinol. 299: 178-187,
2009.
[CrossRef]
[PubMed]
Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev.
19(3):CD004454, 2006.
[PubMed]
Sonneveld E, Jonas A, Meijer OC, Brouwer A, van der Burg B. Glucocorticoid-enhanced expression of dioxin target genes through regulation of the rat
aryl hydrocarbon receptor. Toxicol Sci. 99: 455-469, 2007.
[CrossRef]
[PubMed]
Staud F, Pavek P. Breast cancer resistance protein (BCRP/ABCG2). Int J Biochem Cell Biol. 37: 720-725, 2005.
[CrossRef]
[PubMed]
Stejskalova L, Pavek P. The function of cytochrome P450 1A1 enzyme (CYP1A1) and aryl hydrocarbon receptor (AhR) in the placenta. Curr Pharm
Biotechnol. 12: 715-730, 2011.
[PubMed]
Stejskalova L, Dvorak Z, Pavek P. Endogenous and exogenous ligands of aryl hydrocarbon receptor: current state of art. Curr Drug Metab. 12: 198-212,
2011a.
[CrossRef]
[PubMed]
Stejskalova L, Vecerova L, Perez LM, Vrzal R, Dvorak Z, Nachtigal P, Pavek P. Aryl hydrocarbon receptor (AHR) and aryl hydrocarbon nuclear
translocator (ARNT) expression in human and rat placentas and transcription activity in human trophoblast cultures. Toxicol Sci. 123: 26-36,
2011b.
[CrossRef]
[PubMed]
Vrzal R, Stejskalova L, Monostory K, Maurel P, Bachleda P, Pavek P, Dvorak Z. Dexamethasone controls aryl hydrocarbon receptor (AhR)-mediated CYP1A1
and CYP1A2 expression and activity in primary cultures of human hepatocytes. Chem Biol Interact. 179: 288-296, 2009.
[CrossRef]
[PubMed]
Waddell BJ, Benediktsson R, Brown RW, Seckl JR. Tissue-specific messenger ribonucleic acid expression of 11beta-hydroxysteroid dehydrogenase types 1
and 2 and the glucocorticoid receptor within rat placenta suggests exquisite local control of glucocorticoid action. Endocrinology. 139: 1517-1523,
1998.
[CrossRef]
[PubMed]
Yamamoto J, Ihara K, Nakayama H, Hikino S, Satoh K, Kubo N, Iida T, Fujii Y, Hara T. Characteristic expression of aryl hydrocarbon receptor repressor
gene in human tissues: organ-specific distribution and variable induction patterns in mononuclear cells. Life Sci. 74: 1039-1049, 2004.
[CrossRef]
[PubMed]
Zhu BT, Lee AJ. NADPH-dependent metabolism of 17beta-estradiol and estrone to polar and nonpolar metabolites by human tissues and cytochrome P450
isoforms. Steroids. 70: 225-244, 2005.
[CrossRef]
[PubMed]
|
CITED
0
|
