Related Experiment Videos
Steroid hormone receptors selectively affect transcriptional activation but not basal repression by thyroid hormone
P M Yen1, E C Wilcox, W W Chin
1Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Abstract:
Thyroid hormone receptors (TRs) and steroid hormone receptors belong to a large superfamily of nuclear hormone receptors. The interactions between these receptor subfamilies are poorly understood. In this study, cotransfection assays were used to examine the effects of estrogen and glucocorticoid receptors on TR-mediated repression of basal transcription by unliganded TR and transcriptional activation by liganded TR with two different thyroid hormone response element-containing reporter plasmids. Surprisingly, it was found that steroid hormone receptors blocked T3-mediated transcriptional activation with little or no effect 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 T3-mediated transcriptional activation. These studies strongly suggest divergent pathways for transcriptional activation and basal repression by TRs. Additionally, these studies raise the potential for nuclear hormone receptors to modulate TR-mediated transcriptional activation in steroid hormone-responsive tissues.
Insights
Steroid hormone receptors inhibit thyroid hormone receptor (TR)-mediated gene activation but not repression. This suggests distinct pathways for TR transcriptional regulation and potential cross-talk in hormone-responsive tissues.
Area of Science:
- Molecular Endocrinology
- Nuclear Receptor Signaling
Background:
- Thyroid hormone receptors (TRs) and steroid hormone receptors are nuclear receptors with poorly understood interactions.
- Nuclear receptors regulate gene expression through ligand-dependent and independent mechanisms.
Purpose of the Study:
- To investigate the effects of estrogen and glucocorticoid receptors on TR-mediated transcriptional regulation.
- To elucidate the mechanisms underlying cross-talk between TRs and steroid hormone receptors.
Main Methods:
- Utilized cotransfection assays to assess TR activity.
- Employed reporter plasmids containing thyroid hormone response elements.
Main Results:
- Steroid hormone receptors significantly blocked T3-mediated transcriptional activation by TRs.
- Steroid hormone receptors had minimal impact on basal repression by unliganded TR.
- The inhibitory mechanism appears to involve coactivator titration, not direct DNA binding.
Conclusions:
- TRs exhibit divergent pathways for transcriptional activation and basal repression.
- Nuclear hormone receptors can modulate TR activity, particularly in steroid hormone-responsive tissues.
- Findings highlight potential for complex regulatory interactions within the nuclear receptor superfamily.