Thyroid hormone can increase estrogen-mediated transcription from a consensus estrogen response element in neuroblastoma cells

Xing Zhao, Heather Lorenc, Heather Stephenson, Yunjiao Joy Wang, Dawn Witherspoon, Benita Katzenellenbogen, Donald Pfaff, Nandini Vasudevan

Research output: Contribution to journalArticle

Abstract

Thyroid hormones (T) and estrogens (E) are nuclear receptor ligands with at least two molecular mechanisms of action: (i) relatively slow genomic effects, such as the regulation of transcription by cognate T receptors (TR) and E receptors (ER); and (ii) relatively rapid nongenomic effects, such as kinase activation and calcium release initiated at the membrane by putative membrane receptors. Genomic and nongenomic effects were thought to be disparate and independent. However, in a previous study using a two-pulse paradigm in neuroblastoma cells, we showed that E acting at the membrane could potentiate transcription from an E-driven reporter gene in the nucleus. Because both T and E can have important effects on mood and cognition, it is possible that the two hormones can act synergistically. In this study, we demonstrate that early actions of T via TRα1 and TRβ1 can potentiate E-mediated transcription (genomic effects) from a consensus E response element (ERE)-driven reporter gene in transiently transfected neuroblastoma cells. Such potentiation was reduced by inhibition of mitogen-activated protein kinase. Using phosphomutants of ERα, we also show that probable mitogen-activated protein kinase phosphorylation sites on the ERα, the serines at position 167 and 118, are important in TRβ1-mediated potentiation of ERα-induced transactivation. We suggest that crosstalk between T and E includes potential interactions through both nuclear and membrane-initiated molecular mechanisms of hormone signaling.

Original languageEnglish (US)
Pages (from-to)4890-4895
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number13
DOIs
StatePublished - Mar 29 2005

Fingerprint

Response Elements
Neuroblastoma
Thyroid Hormones
Consensus
Estrogens
Mitogen-Activated Protein Kinases
Reporter Genes
Membranes
Hormones
Nuclear Envelope
Estrogen Receptors
Cognition
Transcriptional Activation
Phosphotransferases
Phosphorylation
Ligands
Calcium

Keywords

  • Crosstalk
  • Nuclear receptors
  • Phosphorylation
  • Synergy

ASJC Scopus subject areas

  • General

Cite this

Thyroid hormone can increase estrogen-mediated transcription from a consensus estrogen response element in neuroblastoma cells. / Zhao, Xing; Lorenc, Heather; Stephenson, Heather; Wang, Yunjiao Joy; Witherspoon, Dawn; Katzenellenbogen, Benita; Pfaff, Donald; Vasudevan, Nandini.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 13, 29.03.2005, p. 4890-4895.

Research output: Contribution to journalArticle

Zhao, Xing ; Lorenc, Heather ; Stephenson, Heather ; Wang, Yunjiao Joy ; Witherspoon, Dawn ; Katzenellenbogen, Benita ; Pfaff, Donald ; Vasudevan, Nandini. / Thyroid hormone can increase estrogen-mediated transcription from a consensus estrogen response element in neuroblastoma cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 13. pp. 4890-4895.
@article{7a0d65d43bb940eab839ee895ac72d7d,
title = "Thyroid hormone can increase estrogen-mediated transcription from a consensus estrogen response element in neuroblastoma cells",
abstract = "Thyroid hormones (T) and estrogens (E) are nuclear receptor ligands with at least two molecular mechanisms of action: (i) relatively slow genomic effects, such as the regulation of transcription by cognate T receptors (TR) and E receptors (ER); and (ii) relatively rapid nongenomic effects, such as kinase activation and calcium release initiated at the membrane by putative membrane receptors. Genomic and nongenomic effects were thought to be disparate and independent. However, in a previous study using a two-pulse paradigm in neuroblastoma cells, we showed that E acting at the membrane could potentiate transcription from an E-driven reporter gene in the nucleus. Because both T and E can have important effects on mood and cognition, it is possible that the two hormones can act synergistically. In this study, we demonstrate that early actions of T via TRα1 and TRβ1 can potentiate E-mediated transcription (genomic effects) from a consensus E response element (ERE)-driven reporter gene in transiently transfected neuroblastoma cells. Such potentiation was reduced by inhibition of mitogen-activated protein kinase. Using phosphomutants of ERα, we also show that probable mitogen-activated protein kinase phosphorylation sites on the ERα, the serines at position 167 and 118, are important in TRβ1-mediated potentiation of ERα-induced transactivation. We suggest that crosstalk between T and E includes potential interactions through both nuclear and membrane-initiated molecular mechanisms of hormone signaling.",
keywords = "Crosstalk, Nuclear receptors, Phosphorylation, Synergy",
author = "Xing Zhao and Heather Lorenc and Heather Stephenson and Wang, {Yunjiao Joy} and Dawn Witherspoon and Benita Katzenellenbogen and Donald Pfaff and Nandini Vasudevan",
year = "2005",
month = "3",
day = "29",
doi = "10.1073/pnas.0501042102",
language = "English (US)",
volume = "102",
pages = "4890--4895",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "13",

}

TY - JOUR

T1 - Thyroid hormone can increase estrogen-mediated transcription from a consensus estrogen response element in neuroblastoma cells

AU - Zhao, Xing

AU - Lorenc, Heather

AU - Stephenson, Heather

AU - Wang, Yunjiao Joy

AU - Witherspoon, Dawn

AU - Katzenellenbogen, Benita

AU - Pfaff, Donald

AU - Vasudevan, Nandini

PY - 2005/3/29

Y1 - 2005/3/29

N2 - Thyroid hormones (T) and estrogens (E) are nuclear receptor ligands with at least two molecular mechanisms of action: (i) relatively slow genomic effects, such as the regulation of transcription by cognate T receptors (TR) and E receptors (ER); and (ii) relatively rapid nongenomic effects, such as kinase activation and calcium release initiated at the membrane by putative membrane receptors. Genomic and nongenomic effects were thought to be disparate and independent. However, in a previous study using a two-pulse paradigm in neuroblastoma cells, we showed that E acting at the membrane could potentiate transcription from an E-driven reporter gene in the nucleus. Because both T and E can have important effects on mood and cognition, it is possible that the two hormones can act synergistically. In this study, we demonstrate that early actions of T via TRα1 and TRβ1 can potentiate E-mediated transcription (genomic effects) from a consensus E response element (ERE)-driven reporter gene in transiently transfected neuroblastoma cells. Such potentiation was reduced by inhibition of mitogen-activated protein kinase. Using phosphomutants of ERα, we also show that probable mitogen-activated protein kinase phosphorylation sites on the ERα, the serines at position 167 and 118, are important in TRβ1-mediated potentiation of ERα-induced transactivation. We suggest that crosstalk between T and E includes potential interactions through both nuclear and membrane-initiated molecular mechanisms of hormone signaling.

AB - Thyroid hormones (T) and estrogens (E) are nuclear receptor ligands with at least two molecular mechanisms of action: (i) relatively slow genomic effects, such as the regulation of transcription by cognate T receptors (TR) and E receptors (ER); and (ii) relatively rapid nongenomic effects, such as kinase activation and calcium release initiated at the membrane by putative membrane receptors. Genomic and nongenomic effects were thought to be disparate and independent. However, in a previous study using a two-pulse paradigm in neuroblastoma cells, we showed that E acting at the membrane could potentiate transcription from an E-driven reporter gene in the nucleus. Because both T and E can have important effects on mood and cognition, it is possible that the two hormones can act synergistically. In this study, we demonstrate that early actions of T via TRα1 and TRβ1 can potentiate E-mediated transcription (genomic effects) from a consensus E response element (ERE)-driven reporter gene in transiently transfected neuroblastoma cells. Such potentiation was reduced by inhibition of mitogen-activated protein kinase. Using phosphomutants of ERα, we also show that probable mitogen-activated protein kinase phosphorylation sites on the ERα, the serines at position 167 and 118, are important in TRβ1-mediated potentiation of ERα-induced transactivation. We suggest that crosstalk between T and E includes potential interactions through both nuclear and membrane-initiated molecular mechanisms of hormone signaling.

KW - Crosstalk

KW - Nuclear receptors

KW - Phosphorylation

KW - Synergy

UR - http://www.scopus.com/inward/record.url?scp=16344380048&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=16344380048&partnerID=8YFLogxK

U2 - 10.1073/pnas.0501042102

DO - 10.1073/pnas.0501042102

M3 - Article

C2 - 15778291

AN - SCOPUS:16344380048

VL - 102

SP - 4890

EP - 4895

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 13

ER -