A thyroid hormone receptor-dependent glucocorticoid induction

Glucocorticoid and thyroid hormones exert their effects in many body tissues by binding to their respective receptors. The search for possible cross-talking mechanisms in overlapping target cells led to the discovery of synergism between a thyroid hormone receptor-binding site and a cryptic glucocorticoid-responsive element. Glucocorticoid responsiveness could only be detected in the presence of thyroid hormone and its receptor. This synergism requires the glucocorticoid receptor (GR) DNA-binding domain and is mediated by the transactivation domains. We found that synergism also occurs when the thyroid hormone receptor is replaced by the retinoic acid receptor or the GR is replaced by the progesterone receptor. Synergism is qualitatively independent of the type of thyroid hormone receptor-binding site and promoter. In several combinations of promoter and response elements, including a retinoic acid response element, T3 induction was only seen in the presence of the cryptic glucocorticoid-responsive element, GR, and glucocorticoids.