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Expression and hormonal regulation of coactivator and corepressor genes
S Misiti1, L Schomburg, P M Yen
1Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. misiti@rascal.med.harvard.edu
Abstract:
Steroid/thyroid/retinoid receptors are members of the nuclear receptor superfamily and ligand-inducible transcription factors. These receptors modulate transcription of various cellular genes, either positively or negatively, by interacting with specific hormone-response elements located in the target gene promoters. Recent data show that nuclear receptors enhance or inhibit transcription by recruiting an array of coactivator and corepressor proteins to the transcription complex. We examined and compared the expression of four coactivator (steroid receptor coactivator-1 and E1A-associated 300-kDa protein) and corepressor (SMRT and N-CoR) genes in a number of tissues including several endocrine glands and cell lines. We also addressed whether their messenger RNA levels are hormonally regulated by studying the effects of thyroid hormone (T3) and estrogen (E2) treatment in rat pituitary cells (GH3) in vitro and in anterior pituitary in vivo. Our studies show that there are distinct tissue-specific expression patterns of these genes. We show that T3 and E2 regulate the expression of steroid receptor coactivator-1 messenger RNA in the anterior pituitary in addition to a gender-related difference. These tissue variations may have physiological implications for heterogeneity of hormone responses that are observed in normal and malignant tissues.
Insights
This study reveals distinct tissue-specific expression of coactivator and corepressor genes. Thyroid hormone (T3) and estrogen (E2) regulate steroid receptor coactivator-1 messenger RNA in the anterior pituitary, showing gender differences.
Area of Science:
- Molecular Biology
- Endocrinology
- Gene Regulation
Background:
- Nuclear receptors, including steroid/thyroid/retinoid receptors, are ligand-inducible transcription factors modulating gene expression.
- They interact with hormone-response elements and recruit coactivator/corepressor proteins to regulate transcription.
- Understanding coactivator and corepressor expression is crucial for comprehending hormone response heterogeneity.
Purpose of the Study:
- To compare the expression patterns of key coactivator (steroid receptor coactivator-1, E1A-associated 300-kDa protein) and corepressor (SMRT, N-CoR) genes across various tissues.
- To investigate the hormonal regulation of these coactivator and corepressor messenger RNAs by thyroid hormone (T3) and estrogen (E2).
- To examine gender-related differences in gene expression within the anterior pituitary.
Main Methods:
- Quantitative analysis of coactivator and corepressor gene expression in multiple endocrine glands and cell lines.
- Hormonal regulation studies using rat pituitary cells (GH3) in vitro and anterior pituitary tissue in vivo.
- Treatment with thyroid hormone (T3) and estrogen (E2) to assess messenger RNA level changes.
Main Results:
- Demonstrated distinct tissue-specific expression profiles for the examined coactivator and corepressor genes.
- Identified hormonal regulation of steroid receptor coactivator-1 messenger RNA by T3 and E2 in the anterior pituitary.
- Revealed a significant gender-related difference in steroid receptor coactivator-1 messenger RNA expression in the anterior pituitary.
Conclusions:
- Tissue-specific expression of coactivators and corepressors contributes to the heterogeneity of hormone responses.
- Hormonal and gender-specific regulation of coactivator expression in the pituitary has significant physiological implications.
- These findings provide insights into differential hormone action in normal and malignant tissues.