Orphan receptors COUP-TF and DAX-1 as targets in disordered CYP17 expression in adrenocortical tumors

H. Shibata, Y. Ikeda, K. Morohashi, T. Mukai, Isao Kurihara, T. Ando, T. Suzuki, S. Kobayashi, K. Hayashi, M. Hayashi, I. Saito, T. Saruta

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Abstract

CYP17 gene transcription is activated by SF-1 binding to a cyclic AMP-responsive sequence within the promoter region of the gene, and its transcription is inhibited by COUP-TF binding to the sequence. Another orphan receptor, DAX-1, is shown to act as a suppressor of SF-1-mediated transcription. We examined the expression level of these orphan receptors in adrenocortical tumors and compared the results with CYP17 expression. CYP17 was highly expressed in cortisol-producing adenomas, whereas COUP-TF and DAX-1 expression levels were very low. In deoxycorticosterone-producing adenomas, on the other hand, CYP17 expression was extremely low, whereas DAX-1 was highly expressed and SF-1 expression was slightly decreased. In conclusion, the reciprocal expression of CYP17 and the transcriptional repressors COUP-TF and DAX-1 indicates that these orphan receptors have a pathophysiologic role in the excessive hormone production in cortisol- and deoxycorticosterone-producing adrenocortical tumors.

Original languageEnglish
Pages (from-to)1039-1044
Number of pages6
JournalEndocrine Research
Volume26
Issue number4
Publication statusPublished - 2000

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Steroid 17-alpha-Hydroxylase
Desoxycorticosterone
Neoplasms
Adenoma
Hydrocortisone
Genetic Promoter Regions
Cyclic AMP
Genes
Hormones

ASJC Scopus subject areas

  • Endocrinology

Cite this

Shibata, H., Ikeda, Y., Morohashi, K., Mukai, T., Kurihara, I., Ando, T., ... Saruta, T. (2000). Orphan receptors COUP-TF and DAX-1 as targets in disordered CYP17 expression in adrenocortical tumors. Endocrine Research, 26(4), 1039-1044.

Orphan receptors COUP-TF and DAX-1 as targets in disordered CYP17 expression in adrenocortical tumors. / Shibata, H.; Ikeda, Y.; Morohashi, K.; Mukai, T.; Kurihara, Isao; Ando, T.; Suzuki, T.; Kobayashi, S.; Hayashi, K.; Hayashi, M.; Saito, I.; Saruta, T.

In: Endocrine Research, Vol. 26, No. 4, 2000, p. 1039-1044.

Research output: Contribution to journalArticle

Shibata, H, Ikeda, Y, Morohashi, K, Mukai, T, Kurihara, I, Ando, T, Suzuki, T, Kobayashi, S, Hayashi, K, Hayashi, M, Saito, I & Saruta, T 2000, 'Orphan receptors COUP-TF and DAX-1 as targets in disordered CYP17 expression in adrenocortical tumors', Endocrine Research, vol. 26, no. 4, pp. 1039-1044.
Shibata, H. ; Ikeda, Y. ; Morohashi, K. ; Mukai, T. ; Kurihara, Isao ; Ando, T. ; Suzuki, T. ; Kobayashi, S. ; Hayashi, K. ; Hayashi, M. ; Saito, I. ; Saruta, T. / Orphan receptors COUP-TF and DAX-1 as targets in disordered CYP17 expression in adrenocortical tumors. In: Endocrine Research. 2000 ; Vol. 26, No. 4. pp. 1039-1044.
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AU - Kurihara, Isao

AU - Ando, T.

AU - Suzuki, T.

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AU - Saito, I.

AU - Saruta, T.

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AB - CYP17 gene transcription is activated by SF-1 binding to a cyclic AMP-responsive sequence within the promoter region of the gene, and its transcription is inhibited by COUP-TF binding to the sequence. Another orphan receptor, DAX-1, is shown to act as a suppressor of SF-1-mediated transcription. We examined the expression level of these orphan receptors in adrenocortical tumors and compared the results with CYP17 expression. CYP17 was highly expressed in cortisol-producing adenomas, whereas COUP-TF and DAX-1 expression levels were very low. In deoxycorticosterone-producing adenomas, on the other hand, CYP17 expression was extremely low, whereas DAX-1 was highly expressed and SF-1 expression was slightly decreased. In conclusion, the reciprocal expression of CYP17 and the transcriptional repressors COUP-TF and DAX-1 indicates that these orphan receptors have a pathophysiologic role in the excessive hormone production in cortisol- and deoxycorticosterone-producing adrenocortical tumors.

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