2,3,7,8-tetrachlorodibenzo-p-dioxin induces CYP1B1 expression in human luteinized granulosa cells.
The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a reproductive toxicant in multiple species; however, mechanisms and direct ovarian effects are poorly understood. DNA microarrays were used to characterize gene expression profiles of human luteinized granulosa cells (HLGCs) exposed to TCDD in primary cultures. Exposure to 10 nM TCDD for 24 h induced a significant increase in CYP1B1, while few other genes responded. TaqMan PCR and Western immunoblotting demonstrated that induction was dose-dependent. Additionally, the microsomal form of catechol-O-methyltransferase (COMT) was highly expressed in HLGCs, along with only fractional amounts of the soluble form. This is the first report of CYP1B1 and COMT expression, and CYP1B1 induction, in cells from the human ovary. The role of CYP1B1 in the oxidative metabolism of estrogens and potential generation of DNA adducts in the ovary may have significant consequences for oocyte quality, corpus luteum function, and ovarian carcinogenesis.
Vidal
J D
JD
Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. justin.2.vidal@gsk.com
Vandevoort
C A
CA
Marcus
C B
CB
Lazarewicz
N R
NR
Conley
A J
AJ
D001189:Aryl Hydrocarbon Hydroxylases; D002394:Catechol O-Methyltransferase / Q000096:biosynthesis; D002478:Cells, Cultured; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015386:Hazardous Substances / Q000633:toxicity*; D006801:Humans; D008184:Luteal Cells / Q000201:enzymology*; D008861:Microsomes / Q000201:enzymology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D013723:Teratogens / Q000633:toxicity*
D004967:Estrogens; D015386:Hazardous Substances; D000072317:Polychlorinated Dibenzodioxins; D013723:Teratogens; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D002394:Catechol O-Methyltransferase