In vitro exposure of porcine prepubertal follicles to 4-chlorobiphenyl (PCB3) and its hydroxylated metabolites: Effects on sex hormone levels and aromatase activity

Anna Ptak; Gabriele Ludewig; Larry Robertson; Hans-Joachim Lehmler; Ewa L Gregoraszczuk

doi:10.1016/j.toxlet.2005.12.001

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In vitro exposure of porcine prepubertal follicles to 4-chlorobiphenyl (PCB3) and its hydroxylated metabolites: Effects on sex hormone levels and aromatase activity

Journal article

Peer reviewed

In vitro exposure of porcine prepubertal follicles to 4-chlorobiphenyl (PCB3) and its hydroxylated metabolites: Effects on sex hormone levels and aromatase activity

Anna Ptak, Gabriele Ludewig, Larry Robertson, Hans-Joachim Lehmler and Ewa L Gregoraszczuk

Toxicology letters, Vol.164(2), pp.113-122

2006

DOI: 10.1016/j.toxlet.2005.12.001

PMID: 16412591

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Abstract

The present study was undertaken to investigate the endocrine disrupting activity of PCB3 and its hydroxylated metabolites 4-OH-PCB3 and 3,4-diOH-PCB3 in ovarian follicle cells derived from prepubertal animals with special emphasis on cytochrome P-450-dependent aromatase (CYP19). Aromatase activity was assayed simply by measuring the production of 17β-estradiol in the culture medium after addition of the substrate (testosterone). Theca interna and granulosa cells were exposed in vitro to 6 ng/ml of test chemicals for 24, 48, 72 and 96 h. PCBs stimulated the conversion of testosterone to estradiol in all treatments. In addition, PCB3, and to a lesser extent its metabolites, decreased progesterone secretion by these cells. This increase in estradiol and simultaneous decrease in progesterone suggests that progesterone is converted to testosterone and further to estradiol. The rank order of potency in estradiol secretion was 3,4-diOH-PCB3 > 4-OH-PCB3 > PCB3. The non-steroidal aromatase inhibitor CGS 16949A abolished this stimulatory activity, and reduced estradiol levels in treatment and control groups below the control levels, verifying that the increased estradiol secretion by follicle cells was due to aromatase activity. We infer that: (1) metabolism of PCB3 does not protect against endocrine disruption and (2) the estrogenic effect of these compounds is due to stimulation of aromatase activity.

Steroid secretion

PCB3

Prepubertal pig ovary

Aromatase activity

Hydroxylated metabolites

Details

Title: Subtitle: In vitro exposure of porcine prepubertal follicles to 4-chlorobiphenyl (PCB3) and its hydroxylated metabolites: Effects on sex hormone levels and aromatase activity
Creators: Anna Ptak - Laboratory of Physiology and Toxicology of Reproduction, Department of Physiology, Institute of Zoology, Jagiellonian University, Ingardena 6, 30-060 Kraków, Poland
Gabriele Ludewig - University of Iowa, Department of Occupational and Environmental Health, College of Public Health, 100 Oakdale Campus 124 IREH, Iowa City, IA 52242-5000, USA
Larry Robertson - University of Iowa, Department of Occupational and Environmental Health, College of Public Health, 100 Oakdale Campus 124 IREH, Iowa City, IA 52242-5000, USA
Hans-Joachim Lehmler - University of Iowa, Department of Occupational and Environmental Health, College of Public Health, 100 Oakdale Campus 124 IREH, Iowa City, IA 52242-5000, USA
Ewa L Gregoraszczuk - Laboratory of Physiology and Toxicology of Reproduction, Department of Physiology, Institute of Zoology, Jagiellonian University, Ingardena 6, 30-060 Kraków, Poland
Resource Type: Journal article
Publication Details: Toxicology letters, Vol.164(2), pp.113-122
DOI: 10.1016/j.toxlet.2005.12.001
PMID: 16412591
NLM abbreviation: Toxicol Lett
ISSN: 0378-4274
eISSN: 1879-3169
Publisher: Elsevier Ireland Ltd
Language: English
Date published: 2006
Academic Unit: Occupational and Environmental Health; Iowa Neuroscience Institute; Iowa Superfund Research Program
Record Identifier: 9984001092102771

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