A low halogenated biphenyl (PCB3) increases CYP1A1 expression and activity via the estrogen receptor beta in the porcine ovary

A Ptak; G Ludewig; E Ł Gregoraszczuk

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A low halogenated biphenyl (PCB3) increases CYP1A1 expression and activity via the estrogen receptor beta in the porcine ovary

Journal article

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A low halogenated biphenyl (PCB3) increases CYP1A1 expression and activity via the estrogen receptor beta in the porcine ovary

A Ptak, G Ludewig and E Ł Gregoraszczuk

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, Vol.59(3), pp.577-588

09/2008

PMID: 18953099

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https://www.jpp.krakow.pl/journal/archive/09_08/pdf/577_09_08_article.pdfView

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Abstract

Polychlorinated biphenyls (PCBs) have been detected at high levels, up to hundreds of pg/ml, in human ovarian follicle fluid. The effect of PCBs on the ovary and the consequences of exposure are largely unknown. We have previously shown that PCB3 (4-chlorobiphenyl) increases the secretion of estradiol and the activity of cytochrome P450s (CYPs) in ovarian follicle cells. Our goal here is to elucidate the mechanism of CYP induction by this congener. Exposure of porcine follicle cells, a co-culture of theca and granulosa cells, to 6 ng/ml of PCB3 caused an increase in CYP1A1 protein and enzymatic activity, in the same manner as exposure to exogenous 17beta-estradiol. No changes were seen in the protein level of the aryl hydrocarbon receptor (AhR), which mediates the first step in the signaling pathway of CYP1A1 induction. However, a strong reduction was seen in the protein level of estrogen receptor beta (ERbeta), while no effect was seen on ERalpha protein levels. These result suggest that: 1) PCB3 acts as an agonist of ERbeta but not the Ah receptor in the ovarian follicles, 2) PCB3 is not only an efficacious inducer of CYP1A1 expression and activity, but also a substrate for this enzyme. Changes in the expression level of CYP1A1 not only alter the intensity of the activity of PCB3, but also the activity of estrogen in the ovary.

Gene Expression Regulation, Enzymologic - drug effects

Coculture Techniques

Receptors, Aryl Hydrocarbon - drug effects

Estrogen Receptor beta - drug effects

Blotting, Western

Granulosa Cells - drug effects

Estrogen Receptor alpha - drug effects

Ovarian Follicle - drug effects

Animals

Benzoflavones - pharmacology

Biphenyl Compounds - pharmacology

Swine

Tamoxifen - pharmacology

Tamoxifen - analogs & derivatives

Female

Ovary - drug effects

Cytochrome P-450 CYP1A1 - biosynthesis

Estradiol - pharmacology

Ovary - metabolism

Theca Cells - drug effects

Details

Title: Subtitle: A low halogenated biphenyl (PCB3) increases CYP1A1 expression and activity via the estrogen receptor beta in the porcine ovary
Creators: A Ptak - Department of Physiology and Toxicology of Reproduction, Institute of Zoology, Jagiellonian University, Krakow, Poland
G Ludewig
E Ł Gregoraszczuk
Resource Type: Journal article
Publication Details: Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, Vol.59(3), pp.577-588
Publisher: Poland
PMID: 18953099
ISSN: 0867-5910
eISSN: 1899-1505
Grant note: P42 ES013661 / NIEHS NIH HHS
Language: English
Date published: 09/2008
Academic Unit: Occupational and Environmental Health; Iowa Superfund Research Program
Record Identifier: 9983997359002771

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