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Differential expression of an orphan receptor COUP-TFI and corepressors in adrenal tumors
1Health Center and Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Abstract:
Recently, it has been shown that CYP17 gene transcription is activated by SF-1 (Steroidogenic Factor-1) binding to a cyclic AMP-responsive sequence within the promoter region of the gene, whereas it is inhibited by COUP-TF (Chicken Ovalbumin Upstream Promoter-Transcription Factor) binding to the sequence. We have shown that transcriptional repression by COUP-TFI is mediated by corepressors, N-CoR (nuclear receptor corepressor) and SMRT (silencing mediator for retinoid and thyroid hormone-receptor). Therefore, we compared the expression of COUP-TFI, N-CoR and SMRT in non-hyperfunctioning adrenocortical adenomas and normal adrenal glands. We found significantly higher expression of COUP-TFI mRNA in non-hyperfunctioning adenomas (n=5, 227+/-18%) than in normal adrenals (n=5, 96+/-4%). Interestingly, the pattern of N-CoR and SMRT expression was different compared with COUP-TFI expression. These data suggest that COUP-TFI, N-CoR, and SMRT may play a differential role in steroid biosynthesis of non-hyperfunctioning adenomas.
Insights
Steroidogenic Factor-1 (SF-1) and Chicken Ovalbumin Upstream Promoter-Transcription Factor (COUP-TF) regulate CYP17 gene transcription. COUP-TF, along with corepressors N-CoR and SMRT, showed higher expression in non-hyperfunctioning adenomas, suggesting a role in steroid biosynthesis.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- CYP17 gene transcription is regulated by Steroidogenic Factor-1 (SF-1) and Chicken Ovalbumin Upstream Promoter-Transcription Factor (COUP-TF).
- Transcriptional repression by COUP-TF is mediated by corepressors nuclear receptor corepressor (N-CoR) and silencing mediator for retinoid and thyroid hormone-receptor (SMRT).
Purpose of the Study:
- To compare the expression of COUP-TFI, N-CoR, and SMRT in non-hyperfunctioning adrenocortical adenomas and normal adrenal glands.
- To investigate the potential role of these factors in the steroid biosynthesis of non-hyperfunctioning adenomas.
Main Methods:
- Quantitative analysis of COUP-TFI, N-CoR, and SMRT mRNA expression.
- Comparison between non-hyperfunctioning adrenocortical adenomas (n=5) and normal adrenal glands (n=5).
Main Results:
- Significantly higher expression of COUP-TFI mRNA was observed in non-hyperfunctioning adenomas (227+/-18%) compared to normal adrenal glands (96+/-4%).
- The expression patterns of N-CoR and SMRT differed from that of COUP-TFI.
Conclusions:
- COUP-TFI, N-CoR, and SMRT may play a differential role in the steroid biosynthesis of non-hyperfunctioning adrenocortical adenomas.
- Further research is warranted to elucidate the specific mechanisms involved.