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

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

doi:10.3109/07435800009048636

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

Endocr Res. 2000 Nov;26(4):1039-44. doi: 10.3109/07435800009048636.

Authors

H Shibata¹, Y Ikeda, K Morohashi, T Mukai, I Kurihara, T Ando, T Suzuki, S Kobayashi, K Hayashi, M Hayashi, I Saito, T Saruta

Affiliation

¹ Health Center and Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. [email protected]

PMID: 11196414
DOI: 10.3109/07435800009048636

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenal Cortex Neoplasms / genetics*
COUP Transcription Factors
DAX-1 Orphan Nuclear Receptor
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / metabolism
Fushi Tarazu Transcription Factors
Gene Expression / physiology*
Homeodomain Proteins
Humans
RNA, Messenger / metabolism*
Receptors, Cytoplasmic and Nuclear
Receptors, Retinoic Acid / genetics*
Receptors, Retinoic Acid / metabolism
Receptors, Steroid*
Repressor Proteins*
Steroid 17-alpha-Hydroxylase / genetics*
Steroid 17-alpha-Hydroxylase / metabolism
Steroidogenic Factor 1
Transcription Factors / genetics*
Transcription Factors / metabolism

Substances

COUP Transcription Factors
DAX-1 Orphan Nuclear Receptor
DNA-Binding Proteins
Fushi Tarazu Transcription Factors
Homeodomain Proteins
NR0B1 protein, human
RNA, Messenger
Receptors, Cytoplasmic and Nuclear
Receptors, Retinoic Acid
Receptors, Steroid
Repressor Proteins
Steroidogenic Factor 1
Transcription Factors
Steroid 17-alpha-Hydroxylase