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

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Keywords

  • Crosstalk
  • Nuclear receptors
  • Phosphorylation
  • Synergy

ASJC Scopus subject areas

  • General

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