Expression profiles of COUP-TF, DAX-1, and SF-1 in the human adrenal gland and adrenocortical tumors

Possible implications in steroidogenesis

Hirotaka Shibata, Yayoi Ikeda, Tokuo Mukai, Ken Ichirou Morohashi, Isao Kurihara, Takashi Ando, Toshihiko Suzuki, Sakiko Kobayashi, Masaru Murai, Ikuo Saito, Takao Saruta

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Chicken ovalbumin upstream promoter-transcription factor (COUP-TF), DAX-1, and steroidogenic factor-1 (SF-1) are orphan members of the nuclear hormone receptor superfamily. COUP-TF and DAX-1 have been shown to negatively regulate the transcriptional activity of SF-1, a steroidogenic cell-specific activator of various steroidogenic cytochrome P450 genes. We therefore examined the expression levels and immunolocalization of COUP-TF, DAX-1, and SF-1 in human adrenal gland (NL) and adrenocortical adenomas, and compared the results with CYP17 expression levels and its enzyme activities to study their potential correlation with adrenocortical steroidogenesis. In NL (n=10), expressions of COUP-TF, DAX-1, and SF-1 were detected in the nuclei of adrenocortical cells, but not in the medulla. In cortisol-producing adenomas causing Cushing syndrome (CS, n=20), CYP17 expression was upregulated (298±2% vs NL 98 ± 4%), whereas expression levels of both COUP-TFs (COUP-TFI, 52±5% vs NL 98±4%; COUP-TFII, 18±4% vs NL 98±4%) and DAX-1 (42±4% vs NL 100±4%) were reduced. In deoxycorticosterone-producing adenomas (DOC, n=2), on the other hand, CYP17 expression was extremely reduced (8 and 12% vs NL 98±4%), whereas DAX-1 expression increased markedly (350 and 360% vs NL 100±4%). Expression levels of SF-1 did not differ between NL (100±8%) and CS (106±10%), but its expression appeared to be decreased in DOC (25 and 20%). These results showed CYP17 expression to be upregulated and downregulated in CS and DOC, respectively, in a manner reciprocal to that of its repressors, COUP-TF and/or DAX-1. In summary, the results indicate that co-localization of COUP-TF, DAX-1, and SF-1 in NL was lost in adrenocortical tumors and that these orphan receptors play an important role in the regulation of steroidogenesis in human adrenals.

Original languageEnglish
Pages (from-to)206-216
Number of pages11
JournalMolecular Genetics and Metabolism
Volume74
Issue number1-2
DOIs
Publication statusPublished - 2001

Fingerprint

COUP Transcription Factors
Steroidogenic Factor 1
Adrenal Glands
Steroid 17-alpha-Hydroxylase
Tumors
Neoplasms
Adenoma
Adrenocortical Adenoma
Desoxycorticosterone
Cushing Syndrome
Enzyme activity
Cytoplasmic and Nuclear Receptors
Cell Nucleus
Cytochrome P-450 Enzyme System
Hydrocortisone
human NR5A1 protein
Down-Regulation
Genes
Enzymes

Keywords

  • Adrenal tumor
  • COUP-TF
  • Cushing syndrome
  • CYP17
  • DAX-1
  • Deoxycorticosterone-producing adenomas
  • SF-1
  • Steroidogenesis

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Endocrinology, Diabetes and Metabolism

Cite this

Expression profiles of COUP-TF, DAX-1, and SF-1 in the human adrenal gland and adrenocortical tumors : Possible implications in steroidogenesis. / Shibata, Hirotaka; Ikeda, Yayoi; Mukai, Tokuo; Morohashi, Ken Ichirou; Kurihara, Isao; Ando, Takashi; Suzuki, Toshihiko; Kobayashi, Sakiko; Murai, Masaru; Saito, Ikuo; Saruta, Takao.

In: Molecular Genetics and Metabolism, Vol. 74, No. 1-2, 2001, p. 206-216.

Research output: Contribution to journalArticle

Shibata, H, Ikeda, Y, Mukai, T, Morohashi, KI, Kurihara, I, Ando, T, Suzuki, T, Kobayashi, S, Murai, M, Saito, I & Saruta, T 2001, 'Expression profiles of COUP-TF, DAX-1, and SF-1 in the human adrenal gland and adrenocortical tumors: Possible implications in steroidogenesis', Molecular Genetics and Metabolism, vol. 74, no. 1-2, pp. 206-216. https://doi.org/10.1006/mgme.2001.3231
Shibata, Hirotaka ; Ikeda, Yayoi ; Mukai, Tokuo ; Morohashi, Ken Ichirou ; Kurihara, Isao ; Ando, Takashi ; Suzuki, Toshihiko ; Kobayashi, Sakiko ; Murai, Masaru ; Saito, Ikuo ; Saruta, Takao. / Expression profiles of COUP-TF, DAX-1, and SF-1 in the human adrenal gland and adrenocortical tumors : Possible implications in steroidogenesis. In: Molecular Genetics and Metabolism. 2001 ; Vol. 74, No. 1-2. pp. 206-216.
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AU - Morohashi, Ken Ichirou

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