TY - JOUR
T1 - Expression profiles of COUP-TF, DAX-1, and SF-1 in the human adrenal gland and adrenocortical tumors
T2 - Possible implications in steroidogenesis
AU - Shibata, Hirotaka
AU - Ikeda, Yayoi
AU - Mukai, Tokuo
AU - Morohashi, Ken Ichirou
AU - Kurihara, Isao
AU - Ando, Takashi
AU - Suzuki, Toshihiko
AU - Kobayashi, Sakiko
AU - Murai, Masaru
AU - Saito, Ikuo
AU - Saruta, Takao
N1 - Funding Information:
We are grateful to Professor Ming-Jer Tsai for generously sharing reagents and for critical comments. We thank Dr. Keiko Honma (Department of Laboratory Medicine, School of Medicine, Keio University, Tokyo, Japan) for measurement of urinary steroid profiles by gas chromatography/mass spectrometry. We also thank Dr. Y. Toyoda (Arida Municipal Hospital, Arida, Wakayama, Japan) for supplying one case of deoxycorticosterone-producing adrenocortical adenoma. We thank Drs. N. Kagawa and M. Waterman (Vanderbilt University, Nashville, TN) for a generous gift of anti-bovine CYP17 antibody. This work was supported by a Grant-in-Aid for Encouragement of Young Scientists, Scientific Research from Japan Society for the Promotion of Science (No. 12770620) (to H. Shibata), by a Grant-in-Aid from Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research (to H. Shibata), Keio Gijuku Academic Development Funds (to H. Shibata), and by a Grant-in-Aid for Research Project for Disorders of Adrenocortical Hormone Production from the Ministry of Health and Welfare, Japan (to T. Saruta).
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
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U2 - 10.1006/mgme.2001.3231
DO - 10.1006/mgme.2001.3231
M3 - Article
C2 - 11592817
AN - SCOPUS:0034788474
SN - 1096-7192
VL - 74
SP - 206
EP - 216
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 1-2
ER -
