Microarray analysis on CYPs expression in pregnant rats after treatment with pregnenolone-16alpha-carbonitrile and phenobarbital.
We previously reported the protein expression profiles of nine cytochrome P450 isozymes (CYPs) in pregnant rat's liver, fetal liver, and placenta after treatment with pregnenolone-16alpha-carbonitrile (PCN), dexamethasone (DEX), or phenobarbital (PB). In this study, the gene expression of 40 CYPs and 2 orphan nuclear receptors for CYP inducers, that is, Nr1i2 (CYP3A subfamily inducible by PCN) and Nr1i3 (CYP2B subfamily inducible by PB), in pregnant rat's liver, fetal liver, and placenta was investigated at one time. Fischer 344 (F344) pregnant rats were daily treated intraperitoneally with 50 mg/kg of PCN or 80 mg/kg of PB from 13 to 16 days of gestation (DG). They were sacrificed on 17 DG, and microarray analysis using Affymetrix Rat Expression Array 230A was performed. Ten genes expression significantly increased in dam's liver in PCN group, and seven genes expression in PB group. On the other hand, four genes expression increased in fetal liver in PCN group, and three genes expression increased in PB group. Being common to dam's and fetal livers, the gene expression of Cyp3A1 (CYP3A subfamily) and cytochrome P-450e (CYP2B subfamily) increased in both PCN and PB groups. In placenta, the expression of Cyp3A1 gene was significantly induced in PB group, and it also showed a tendency to increase in PCN group. The expression of Nr1i2 gene was significantly elevated only in dam's liver of PCN group, while the expression of Nr1i3 gene showed no changes in all groups. The results of the present study of 40 CYPs gene expression mostly corresponded to our previous reports on 9 CYPs protein expression.
Ejiri
Noriko
N
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan.
Katayama
Kei-ichi
K
Kiyosawa
Naoki
N
Baba
Yasuko
Y
Doi
Kunio
K
D000818:Animals; D000090702:Constitutive Androstane Receptor; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D004790:Enzyme Induction / Q000187:drug effects* / Q000235:genetics; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000201:enzymology; D007274:Injections, Intraperitoneal; D007527:Isoenzymes; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000201:enzymology; D010634:Phenobarbital / Q000008:administration & dosage / Q000494:pharmacology*; D010920:Placenta / Q000187:drug effects / Q000201:enzymology; D011247:Pregnancy; D011285:Pregnenolone Carbonitrile / Q000008:administration & dosage / Q000494:pharmacology*; D040081:Protein Array Analysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D000090702:Constitutive Androstane Receptor; D017931:DNA Primers; D007527:Isoenzymes; C000716329:Nr1i3 protein, rat; D012333:RNA, Messenger; D011285:Pregnenolone Carbonitrile; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital