STEROID-HORMONE RECEPTORS SELECTIVELY AFFECT TRANSCRIPTIONAL ACTIVATION BUT NOT BASAL REPRESSION BY THYROID-HORMONE RECEPTORS

Thyroid hormone receptors (TRs) and steroid hormone receptors belong t o a large superfamily of nuclear hormone receptors. The interactions b etween these receptor subfamilies are poorly understood. In this study , cotransfection assays were used to examine the effects of estrogen a nd glucocorticoid receptors on TR-mediated repression of basal transcr iption by unliganded TR and transcriptional activation by liganded TR with two different thyroid hormone response element-containing reporte r plasmids. Surprisingly, it was found that steroid hormone receptors blocked T-3-mediated transcriptional activation with little or no effe ct on basal repression by unliganded TR. The mechanism for blocking TR -mediated transcriptional activation does not require steroid hormone receptor binding to the thyroid hormone response element but, rather, may involve titration of a critical coactivator(s) required for T-3-me diated transcriptional activation. These studies strongly suggest dive rgent pathways for transcriptional activation and basal repression by TRs. Additionally, these studies raise the potential for nuclear hormo ne receptors to modulate TR-mediated transcriptional activation in ste roid hormone-responsive tissues.