Nuclear receptors and co-regulators in adrenal tumors

Hirotaka Shibata, Sakiko Kobayashi, Isao Kurihara, Ikuo Saito, Takao Saruta

研究成果: Article査読

12 被引用数 (Scopus)

抄録

We have reported that excessive steroid hormone production in adrenal cortical tumors results from the disordered expression and activity of specific steroidogenic enzymes. Since no genetic mutations in these steroidogenic enzymes have as yet been identified, disordered expression at the transcription level may be crucial for excessive hormone production in adrenocortical tumors. Nuclear receptors SF-1 and COUP-TF/DAX-1 have been shown to activate and repress, respectively, the transcription of CYP17 gene in a mutually exclusive manner in Y-1 cells. Interestingly, the expression of COUP-TF and DAX-1 is significantly decreased in the cortisol-producing adenomas, in which CYP17 is overexpressed. Conversely, DAX-1 is highly expressed in deoxycorticosterone-producing adenomas, where CYP17 expression is almost absent. These expression profiles indicate the possibility that COUP-TF and DAX-1 play important roles in the transcriptional repression of CYP17 in adrenal tumors. To clarify the mechanisms of COUP-TF-mediated repression, we therefore screened for COUP-TF-interacting proteins using a yeast two-hybrid system from a cortisol-producing adenoma cDNA library. We then cloned a novel COUP-TF-interacting protein-1 (CIP-1), which interacts with COUP-TFI, COUP-TFII, and SF-1. Functionally, CIP-1 can act as a transcriptional co-repressor for COUP-TF repression activity. CIP-1 expression profiles parallel those of COUP-TFI in steroidogenic tissues, strongly suggesting that, together, COUP-TFI and CIP-1 play an important role in steroidogenesis.

本文言語English
ページ(範囲)85-93
ページ数9
ジャーナルHormone Research
59
SUPPL. 1
DOI
出版ステータスPublished - 2003 2 13

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 内分泌学

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