Crosstalk between oestrogen receptors and thyroid hormone receptor isoforms results in differential regulation of the preproenkephalin gene.

摘要: Nuclear receptors are ligand-activated transcription factors, which have the potential to integrate internal metabolic events in an organism, with consequences for control of behaviour. Previous studies from this laboratory shown that thyroid hormone receptor (TR) isoforms can inhibit oestrogen (ER)alpha-mediated induction preproenkephalin (PPE) gene expression hypothalamus. Also, administration inhibits lordosis, a behaviour facilitated by PPE expression. We examined effect multiple ligand-binding TR on ER-mediated transient transfection assays CV-1 cells. On natural promoter fragment containing two putative response elements (EREs), both ER alpha and beta mediate four five-fold oestrogen. Cotransfection 1 along inhibited transactivation approximately 50%. However, cotransfection either or 2 plasmids produced no mediated PPE. Therefore, under these experimental conditions, interactions single isoform specific individual isoform. Transfection DNA-binding mutant could also transactivation, suggesting competition binding ERE may not be exclusive mechanism inhibition. Data coactivator, SRC-1, suggested coactivator squelching participate In dramatic contrast, when is cotransfected, stimulated beta-mediated eight-fold over levels. This first study revealing among nuclear neuroendocrine promoter. These data suggest combinatorics allow forms flexible regulations service integration.