COUP-TFI expression in human adrenocortical adenomas: Possible role in steroidogenesis

Hirotaka Shibata, Takashi Ando, Toshihiko Suzuki, Isao Kurihara, Koichi Hayashi, Matsuhiko Hayashi, Ikuo Saito, Masaru Murai, Takao Saruta

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI) is an orphan nuclear receptor essential for neurogenesis, organogenesis, and cell fate determination. CYP17 gene transcription has recently been shown to be activated by SF-1 (steroidogenic factor-1) binding to a cyclic AMP- responsive sequence within the promoter region of the gene, and inhibited by COUP-TF binding to the sequence. Thus, COUP-TF and SF-1 act as a transcriptional repressor and activator, respectively, of CYP17 gene expression. Transcriptional repression by COUP-TFI is mediated by corepressors, N-CoR (nuclear receptor-corepressor) and SMRT (silencing mediator for retinoid and thyroid hormone-receptor), whereas transcriptional activation by SF-1 is mediated by coactivator SRC-1 (steroid receptor coactivator-1). We therefore examined the expression of COUP-TFI, SF-1, SRC- 1, N-CoR, and SMRT in a variety of adrenocortical adenomas and compared the results with CYP17 mRNA levels. We found significantly high COUP-TFI mRNA expression in nonfunctional adenomas (n=8: 220±16%; normal 96±4%), a deoxycorticosterone-producing adenoma (n=1: 200%), and a pre-clinical Cushing's adenoma (n=1: 280%), intermediate COUP-TFI expression in cortisol- producing adenomas (n=8: 63±5%), and low COUP-TFI expression in aldosterone- producing adenomas (n=8: 49±4%). In contrast to COUP-TFI, SF-1 mRNA expression did not vary significantly among adrenals. We did not detect the expected negative correlation between COUP-TFI and CYP17 mRNA levels in adrenocortical adenomas. High COUP-TFI expression was associated with a nonfunctioning phenotype. Interestingly, the pattern of COUP-TFI expression was similar to the profile of N-CoR expression, but not of SMRT expression. These results indicate that COUP-TFI and N-CoR may play a role in steroidogenesis by human adrenocortical adenomas.

Original languageEnglish
Pages (from-to)4520-4523
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Volume83
Issue number12
DOIs
Publication statusPublished - 1998

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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