Nuclear receptors and co-regulators in adrenal tumors

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

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)85-93
Number of pages9
JournalHormone Research
Volume59
Issue numberSUPPL. 1
DOIs
Publication statusPublished - 2003

Fingerprint

COUP Transcription Factors
Glandular and Epithelial Neoplasms
Steroid 17-alpha-Hydroxylase
Cytoplasmic and Nuclear Receptors
Adenoma
Hydrocortisone
Hormones
Co-Repressor Proteins
Desoxycorticosterone
Two-Hybrid System Techniques
Enzymes
Gene Library
Neoplasms
Steroids
Mutation
Genes

Keywords

  • Adrenal tumor
  • COUP-TF
  • CYP11B2
  • CYP17
  • DAX-1
  • Nuclear receptor
  • SF-1

ASJC Scopus subject areas

  • Endocrinology

Cite this

Shibata, H., Kobayashi, S., Kurihara, I., Saito, I., & Saruta, T. (2003). Nuclear receptors and co-regulators in adrenal tumors. Hormone Research, 59(SUPPL. 1), 85-93. https://doi.org/10.1159/000067830

Nuclear receptors and co-regulators in adrenal tumors. / Shibata, Hirotaka; Kobayashi, Sakiko; Kurihara, Isao; Saito, Ikuo; Saruta, Takao.

In: Hormone Research, Vol. 59, No. SUPPL. 1, 2003, p. 85-93.

Research output: Contribution to journalArticle

Shibata, H, Kobayashi, S, Kurihara, I, Saito, I & Saruta, T 2003, 'Nuclear receptors and co-regulators in adrenal tumors', Hormone Research, vol. 59, no. SUPPL. 1, pp. 85-93. https://doi.org/10.1159/000067830
Shibata, Hirotaka ; Kobayashi, Sakiko ; Kurihara, Isao ; Saito, Ikuo ; Saruta, Takao. / Nuclear receptors and co-regulators in adrenal tumors. In: Hormone Research. 2003 ; Vol. 59, No. SUPPL. 1. pp. 85-93.
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