In vitro exposure to environmental tobacco smoke induces CYP1B1 expression in human luteinized granulosa cells.
Women smokers and women exposed to environmental tobacco smoke (ETS) have reduced ovarian function as evidenced by an earlier menopause, reduced follicular numbers, decreased levels of circulating estradiol, and decreased conception rates; however, the mechanism of action of altered ovarian function by ETS is poorly understood. The direct effects of ETS were evaluated using human luteinized granulosa cells (HLGCs) exposed to ETS in primary cell culture. Exposure to ETS caused a decrease in both estradiol and progesterone production. There was a concentration dependent increase in CYP1B1 gene and protein expression without a change in catechol-O-methyltransferase (COMT) expression. This is the first report of CYP1B1 induction secondary to ETS exposure in cells from the human ovary. CYP1B1 metabolizes both endogenous estrogens and polyaromatic hydrocarbons in ETS to a variety of reactive species and may contribute to the complex effects of ETS on ovarian function.
Vidal
Justin D
JD
Population Health and Reproduction, University of California at Davis, Davis, CA 95616, USA. justin.2.vidal@gsk.com
VandeVoort
Catherine A
CA
Marcus
Craig B
CB
Lazarewicz
Nicolas R
NR
Conley
Alan J
AJ
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D002478:Cells, Cultured; D065633:Cytochrome P-450 CYP1B1; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D034461:Luteinization / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014028:Tobacco Smoke Pollution / Q000032:analysis*
D004965:Estrogen Antagonists; D000072317:Polychlorinated Dibenzodioxins; D014028:Tobacco Smoke Pollution; D011374:Progesterone; D004958:Estradiol; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D002394:Catechol O-Methyltransferase