TY - JOUR
T1 - Orphan receptors COUP-TF and DAX-1 as targets in disordered CYP17 expression in adrenocortical tumors
AU - Shibata, H.
AU - Ikeda, Y.
AU - Morohashi, K.
AU - Mukai, T.
AU - Kurihara, I.
AU - Ando, T.
AU - Suzuki, T.
AU - Kobayashi, S.
AU - Hayashi, K.
AU - Hayashi, M.
AU - Saito, I.
AU - Saruta, T.
N1 - Funding Information:
This work is supported by a Grant-in-Aid for Encouragcment of Young Scientists, Scientific Research from Japan Society for the Promotion of Science (No. 12770620) to H.Shibata, and by a Grant-in-Aid for Research Project for Disorders of Adrenocortical Hormonc Production from thc Ministry of Hcalth and Welfare, Japan to T. Saruta. Correspondence shoiild be addressed to: Hirotaka Shibata, M.D., Ph. D., Assistant Professor. Health Center and Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanoniachi, Shinjuku-ku, Tokyo 160- 8582, Japan. E-mail: hiro-405@cb3.so-net.ne.jp
PY - 2000
Y1 - 2000
N2 - 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.
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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U2 - 10.3109/07435800009048636
DO - 10.3109/07435800009048636
M3 - Article
C2 - 11196414
AN - SCOPUS:0034519867
SN - 0743-5800
VL - 26
SP - 1039
EP - 1044
JO - Endocrine Research
JF - Endocrine Research
IS - 4
ER -