Transcriptional activation of the membrane-bound progesterone receptor (mPR) by dioxin, in endocrine-responsive tissues

Ornella Selmin, Patricia A. Thorne, Francoise M. Blachere, Paula D. Johnson, Donato Romagnolo

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

We originally identified the membrane-bound progesterone receptor (mPR) using a screening for genes differentially expressed in liver of rats exposed to dioxin. Recent findings have suggested a role for the mPR in sperm cells, ovary, and brain; however, its mechanisms of action are largely unknown. In this study, we examined the expression pattern of the mPR in liver of rats exposed to dioxin and identified possible mechanisms of its regulation. We observed that mPR expression was induced by dioxin, but was also dependent on the hormonal responsiveness of the tissue. In particular, in male, but not female liver, dioxin induced the expression of the mPR. However, in control, untreated female liver the level of mPR transcript was higher than in control males. Moreover, in breast cancer cells MCF-7 dioxin induced mPR expression. Promoter studies using the luciferase assay indicated that a fragment of ∼350 bp of the mPR promoter was able to induce luciferase activity in the presence of dioxin, suggesting that the presumptive XREs sites contained in this mPR promoter region are responsive to dioxin. Analysis of mPR protein level confirmed the results observed at the RNA level, both in rat liver and MCF-7 cells. Taken together, these observations suggest the existence of a novel cross-talk between steroid and aromatic hydrocarbon receptors (AhR), and underline the importance of the mPR as a mediator of physiologic effects of the sex hormones.

Original languageEnglish (US)
Pages (from-to)166-174
Number of pages9
JournalMolecular Reproduction and Development
Volume70
Issue number2
DOIs
StatePublished - Feb 2005

Fingerprint

Dioxins
Progesterone Receptors
Transcriptional Activation
Membranes
Liver
MCF-7 Cells
Luciferases
Aromatic Hydrocarbons
Gonadal Steroid Hormones
Genetic Promoter Regions
Spermatozoa
Ovary
Steroids
RNA
Breast Neoplasms

Keywords

  • Aromatic hydrocarbon receptor
  • Endocrine disrupters
  • Estrogen receptor
  • Membrane-bound steroid receptor

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology
  • Cell Biology

Cite this

Transcriptional activation of the membrane-bound progesterone receptor (mPR) by dioxin, in endocrine-responsive tissues. / Selmin, Ornella; Thorne, Patricia A.; Blachere, Francoise M.; Johnson, Paula D.; Romagnolo, Donato.

In: Molecular Reproduction and Development, Vol. 70, No. 2, 02.2005, p. 166-174.

Research output: Contribution to journalArticle

@article{8f31db56bcac470081e261ee596e4b62,
title = "Transcriptional activation of the membrane-bound progesterone receptor (mPR) by dioxin, in endocrine-responsive tissues",
abstract = "We originally identified the membrane-bound progesterone receptor (mPR) using a screening for genes differentially expressed in liver of rats exposed to dioxin. Recent findings have suggested a role for the mPR in sperm cells, ovary, and brain; however, its mechanisms of action are largely unknown. In this study, we examined the expression pattern of the mPR in liver of rats exposed to dioxin and identified possible mechanisms of its regulation. We observed that mPR expression was induced by dioxin, but was also dependent on the hormonal responsiveness of the tissue. In particular, in male, but not female liver, dioxin induced the expression of the mPR. However, in control, untreated female liver the level of mPR transcript was higher than in control males. Moreover, in breast cancer cells MCF-7 dioxin induced mPR expression. Promoter studies using the luciferase assay indicated that a fragment of ∼350 bp of the mPR promoter was able to induce luciferase activity in the presence of dioxin, suggesting that the presumptive XREs sites contained in this mPR promoter region are responsive to dioxin. Analysis of mPR protein level confirmed the results observed at the RNA level, both in rat liver and MCF-7 cells. Taken together, these observations suggest the existence of a novel cross-talk between steroid and aromatic hydrocarbon receptors (AhR), and underline the importance of the mPR as a mediator of physiologic effects of the sex hormones.",
keywords = "Aromatic hydrocarbon receptor, Endocrine disrupters, Estrogen receptor, Membrane-bound steroid receptor",
author = "Ornella Selmin and Thorne, {Patricia A.} and Blachere, {Francoise M.} and Johnson, {Paula D.} and Donato Romagnolo",
year = "2005",
month = "2",
doi = "10.1002/mrd.20090",
language = "English (US)",
volume = "70",
pages = "166--174",
journal = "Molecular Reproduction and Development",
issn = "1040-452X",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Transcriptional activation of the membrane-bound progesterone receptor (mPR) by dioxin, in endocrine-responsive tissues

AU - Selmin, Ornella

AU - Thorne, Patricia A.

AU - Blachere, Francoise M.

AU - Johnson, Paula D.

AU - Romagnolo, Donato

PY - 2005/2

Y1 - 2005/2

N2 - We originally identified the membrane-bound progesterone receptor (mPR) using a screening for genes differentially expressed in liver of rats exposed to dioxin. Recent findings have suggested a role for the mPR in sperm cells, ovary, and brain; however, its mechanisms of action are largely unknown. In this study, we examined the expression pattern of the mPR in liver of rats exposed to dioxin and identified possible mechanisms of its regulation. We observed that mPR expression was induced by dioxin, but was also dependent on the hormonal responsiveness of the tissue. In particular, in male, but not female liver, dioxin induced the expression of the mPR. However, in control, untreated female liver the level of mPR transcript was higher than in control males. Moreover, in breast cancer cells MCF-7 dioxin induced mPR expression. Promoter studies using the luciferase assay indicated that a fragment of ∼350 bp of the mPR promoter was able to induce luciferase activity in the presence of dioxin, suggesting that the presumptive XREs sites contained in this mPR promoter region are responsive to dioxin. Analysis of mPR protein level confirmed the results observed at the RNA level, both in rat liver and MCF-7 cells. Taken together, these observations suggest the existence of a novel cross-talk between steroid and aromatic hydrocarbon receptors (AhR), and underline the importance of the mPR as a mediator of physiologic effects of the sex hormones.

AB - We originally identified the membrane-bound progesterone receptor (mPR) using a screening for genes differentially expressed in liver of rats exposed to dioxin. Recent findings have suggested a role for the mPR in sperm cells, ovary, and brain; however, its mechanisms of action are largely unknown. In this study, we examined the expression pattern of the mPR in liver of rats exposed to dioxin and identified possible mechanisms of its regulation. We observed that mPR expression was induced by dioxin, but was also dependent on the hormonal responsiveness of the tissue. In particular, in male, but not female liver, dioxin induced the expression of the mPR. However, in control, untreated female liver the level of mPR transcript was higher than in control males. Moreover, in breast cancer cells MCF-7 dioxin induced mPR expression. Promoter studies using the luciferase assay indicated that a fragment of ∼350 bp of the mPR promoter was able to induce luciferase activity in the presence of dioxin, suggesting that the presumptive XREs sites contained in this mPR promoter region are responsive to dioxin. Analysis of mPR protein level confirmed the results observed at the RNA level, both in rat liver and MCF-7 cells. Taken together, these observations suggest the existence of a novel cross-talk between steroid and aromatic hydrocarbon receptors (AhR), and underline the importance of the mPR as a mediator of physiologic effects of the sex hormones.

KW - Aromatic hydrocarbon receptor

KW - Endocrine disrupters

KW - Estrogen receptor

KW - Membrane-bound steroid receptor

UR - http://www.scopus.com/inward/record.url?scp=11244321561&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=11244321561&partnerID=8YFLogxK

U2 - 10.1002/mrd.20090

DO - 10.1002/mrd.20090

M3 - Article

C2 - 15570619

AN - SCOPUS:11244321561

VL - 70

SP - 166

EP - 174

JO - Molecular Reproduction and Development

JF - Molecular Reproduction and Development

SN - 1040-452X

IS - 2

ER -