2,3,7,8-Tetrachlorodibenzo-p-dioxin activates the aryl hydrocarbon receptor and alters sex steroid hormone secretion without affecting growth of mouse antral follicles in vitro

Bethany N. Karman, Mallikarjuna S. Basavarajappa, Zelieann R. Craig, Jodi A Flaws

Research output: Contribution to journalArticle

Abstract

The persistent environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an ovarian toxicant. These studies were designed to characterize the actions of TCDD on steroidogenesis and growth of intact mouse antral follicles in vitro. Specifically, these studies tested the hypothesis that TCDD exposure leads to decreased sex hormone production/secretion by antral follicles as well as decreased growth of antral follicles in vitro. Since TCDD acts through binding to the aryl hydrocarbon receptor (AHR), and the AHR has been identified as an important factor in ovarian function, we also conducted experiments to confirm the presence and activation of the AHR in our tissue culture system. To do so, we exposed mouse antral follicles for 96. h to a series of TCDD doses previously shown to have effects on ovarian tissues and cells in culture, which also encompass environmentally relevant and pharmacological exposures (0.1-100. nM), to determine a dose response for TCDD in our culture system for growth, hormone production, and expression of the Ahr and Cyp1b1. The results indicate that TCDD decreases progesterone, androstenedione, testosterone, and estradiol levels in a non-monotonic dose response manner without altering growth of antral follicles. The addition of pregnenolone substrate (10. μM) restores hormone levels to control levels. Additionally, Cyp1b1 levels were increased by 3-4 fold regardless of the dose of TCDD exposure, evidence of AHR activation. Overall, these data indicate that TCDD may act prior to pregnenolone formation and through AHR transcriptional control of Cyp1b1, leading to decreased hormone levels without affecting growth of antral follicles.

Original languageEnglish (US)
Pages (from-to)88-96
Number of pages9
JournalToxicology and Applied Pharmacology
Volume261
Issue number1
DOIs
StatePublished - May 15 2012

Fingerprint

Aryl Hydrocarbon Receptors
Gonadal Steroid Hormones
Growth
Pregnenolone
Chemical activation
Hormones
Polychlorinated Dibenzodioxins
In Vitro Techniques
Antral
1,4-dioxin
Tissue culture
Androstenedione
Level control
Growth Hormone
Progesterone
Testosterone
Estradiol
Cell Culture Techniques
Pharmacology
Impurities

Keywords

  • Antral follicle
  • Aryl hydrocarbon receptor
  • Ovary
  • Proliferation
  • Steroidogenesis
  • TCDD

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

2,3,7,8-Tetrachlorodibenzo-p-dioxin activates the aryl hydrocarbon receptor and alters sex steroid hormone secretion without affecting growth of mouse antral follicles in vitro. / Karman, Bethany N.; Basavarajappa, Mallikarjuna S.; Craig, Zelieann R.; Flaws, Jodi A.

In: Toxicology and Applied Pharmacology, Vol. 261, No. 1, 15.05.2012, p. 88-96.

Research output: Contribution to journalArticle

@article{b96fb6ca2d184a5581489f6659962c23,
title = "2,3,7,8-Tetrachlorodibenzo-p-dioxin activates the aryl hydrocarbon receptor and alters sex steroid hormone secretion without affecting growth of mouse antral follicles in vitro",
abstract = "The persistent environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an ovarian toxicant. These studies were designed to characterize the actions of TCDD on steroidogenesis and growth of intact mouse antral follicles in vitro. Specifically, these studies tested the hypothesis that TCDD exposure leads to decreased sex hormone production/secretion by antral follicles as well as decreased growth of antral follicles in vitro. Since TCDD acts through binding to the aryl hydrocarbon receptor (AHR), and the AHR has been identified as an important factor in ovarian function, we also conducted experiments to confirm the presence and activation of the AHR in our tissue culture system. To do so, we exposed mouse antral follicles for 96. h to a series of TCDD doses previously shown to have effects on ovarian tissues and cells in culture, which also encompass environmentally relevant and pharmacological exposures (0.1-100. nM), to determine a dose response for TCDD in our culture system for growth, hormone production, and expression of the Ahr and Cyp1b1. The results indicate that TCDD decreases progesterone, androstenedione, testosterone, and estradiol levels in a non-monotonic dose response manner without altering growth of antral follicles. The addition of pregnenolone substrate (10. μM) restores hormone levels to control levels. Additionally, Cyp1b1 levels were increased by 3-4 fold regardless of the dose of TCDD exposure, evidence of AHR activation. Overall, these data indicate that TCDD may act prior to pregnenolone formation and through AHR transcriptional control of Cyp1b1, leading to decreased hormone levels without affecting growth of antral follicles.",
keywords = "Antral follicle, Aryl hydrocarbon receptor, Ovary, Proliferation, Steroidogenesis, TCDD",
author = "Karman, {Bethany N.} and Basavarajappa, {Mallikarjuna S.} and Craig, {Zelieann R.} and Flaws, {Jodi A}",
year = "2012",
month = "5",
day = "15",
doi = "10.1016/j.taap.2012.03.015",
language = "English (US)",
volume = "261",
pages = "88--96",
journal = "Toxicology and Applied Pharmacology",
issn = "0041-008X",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - 2,3,7,8-Tetrachlorodibenzo-p-dioxin activates the aryl hydrocarbon receptor and alters sex steroid hormone secretion without affecting growth of mouse antral follicles in vitro

AU - Karman, Bethany N.

AU - Basavarajappa, Mallikarjuna S.

AU - Craig, Zelieann R.

AU - Flaws, Jodi A

PY - 2012/5/15

Y1 - 2012/5/15

N2 - The persistent environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an ovarian toxicant. These studies were designed to characterize the actions of TCDD on steroidogenesis and growth of intact mouse antral follicles in vitro. Specifically, these studies tested the hypothesis that TCDD exposure leads to decreased sex hormone production/secretion by antral follicles as well as decreased growth of antral follicles in vitro. Since TCDD acts through binding to the aryl hydrocarbon receptor (AHR), and the AHR has been identified as an important factor in ovarian function, we also conducted experiments to confirm the presence and activation of the AHR in our tissue culture system. To do so, we exposed mouse antral follicles for 96. h to a series of TCDD doses previously shown to have effects on ovarian tissues and cells in culture, which also encompass environmentally relevant and pharmacological exposures (0.1-100. nM), to determine a dose response for TCDD in our culture system for growth, hormone production, and expression of the Ahr and Cyp1b1. The results indicate that TCDD decreases progesterone, androstenedione, testosterone, and estradiol levels in a non-monotonic dose response manner without altering growth of antral follicles. The addition of pregnenolone substrate (10. μM) restores hormone levels to control levels. Additionally, Cyp1b1 levels were increased by 3-4 fold regardless of the dose of TCDD exposure, evidence of AHR activation. Overall, these data indicate that TCDD may act prior to pregnenolone formation and through AHR transcriptional control of Cyp1b1, leading to decreased hormone levels without affecting growth of antral follicles.

AB - The persistent environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an ovarian toxicant. These studies were designed to characterize the actions of TCDD on steroidogenesis and growth of intact mouse antral follicles in vitro. Specifically, these studies tested the hypothesis that TCDD exposure leads to decreased sex hormone production/secretion by antral follicles as well as decreased growth of antral follicles in vitro. Since TCDD acts through binding to the aryl hydrocarbon receptor (AHR), and the AHR has been identified as an important factor in ovarian function, we also conducted experiments to confirm the presence and activation of the AHR in our tissue culture system. To do so, we exposed mouse antral follicles for 96. h to a series of TCDD doses previously shown to have effects on ovarian tissues and cells in culture, which also encompass environmentally relevant and pharmacological exposures (0.1-100. nM), to determine a dose response for TCDD in our culture system for growth, hormone production, and expression of the Ahr and Cyp1b1. The results indicate that TCDD decreases progesterone, androstenedione, testosterone, and estradiol levels in a non-monotonic dose response manner without altering growth of antral follicles. The addition of pregnenolone substrate (10. μM) restores hormone levels to control levels. Additionally, Cyp1b1 levels were increased by 3-4 fold regardless of the dose of TCDD exposure, evidence of AHR activation. Overall, these data indicate that TCDD may act prior to pregnenolone formation and through AHR transcriptional control of Cyp1b1, leading to decreased hormone levels without affecting growth of antral follicles.

KW - Antral follicle

KW - Aryl hydrocarbon receptor

KW - Ovary

KW - Proliferation

KW - Steroidogenesis

KW - TCDD

UR - http://www.scopus.com/inward/record.url?scp=84860515849&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860515849&partnerID=8YFLogxK

U2 - 10.1016/j.taap.2012.03.015

DO - 10.1016/j.taap.2012.03.015

M3 - Article

C2 - 22483799

AN - SCOPUS:84860515849

VL - 261

SP - 88

EP - 96

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

SN - 0041-008X

IS - 1

ER -