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 TRalpha1 and TRbeta1 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 ERalpha, we also show that probable mitogen-activated protein kinase phosphorylation sites on the ERalpha, the serines at position 167 and 118, are important in TRbeta1-mediated potentiation of ERalpha-induced transactivation. We suggest that crosstalk between T and E includes potential interactions through both nuclear and membrane-initiated molecular mechanisms of hormone signaling.
authors.affiliation: Department of Biology, Pennsylvania State University, University Park, PA 16801, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhao
authors.forename: Heather
authors.initials: H
authors.lastname: Lorenc
authors.forename: Heather
authors.initials: H
authors.lastname: Stephenson
authors.forename: Yunjiao Joy
authors.initials: YJ
authors.lastname: Wang
authors.forename: Dawn
authors.initials: D
authors.lastname: Witherspoon
authors.forename: Benita
authors.initials: B
authors.lastname: Katzenellenbogen
authors.forename: Donald
authors.initials: D
authors.lastname: Pfaff
authors.forename: Nandini
authors.initials: N
authors.lastname: Vasudevan
mesh_terms: D000704:Analysis of Variance; D004967:Estrogens / Q000378:metabolism* / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D008156:Luciferases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D020218:Response Elements / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics / Q000378:metabolism; D037042:Thyroid Hormone Receptors beta / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism* / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase
chemical_list: D004967:Estrogens; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D008156:Luciferases; D020928:Mitogen-Activated Protein Kinases; D001616:beta-Galactosidase