Expression profiles of COUP-TF, DAX-1, and SF-1 in the human adrenal glandand adrenocortical tumors: Possible implications in steroidogenesis

Citation
H. Shibata et al., Expression profiles of COUP-TF, DAX-1, and SF-1 in the human adrenal glandand adrenocortical tumors: Possible implications in steroidogenesis, MOL GEN MET, 74(1-2), 2001, pp. 206-216
Citations number
52
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
MOLECULAR GENETICS AND METABOLISM
ISSN journal
1096-7192 → ACNP
Volume
74
Issue
1-2
Year of publication
2001
Pages
206 - 216
Database
ISI
SICI code
1096-7192(200109/10)74:1-2<206:EPOCDA>2.0.ZU;2-O
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 regu late the transcriptional activity of SF-1, a steroidogenic cell-specific ac tivator of various steroidogenic cytochrome P450 genes. We therefore examin ed 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 the ir potential correlation with adrenocortical steroidogenesis. In NL (n = 10 ), expressions of COUP-TF, DAX-1, and SF-1 were detected in the nuclei of a drenocortical cells, but not in the medulla. In cortisol-producing adenomas causing Cushing syndrome (CS, n = 20), CYP17 expression was upregulated (2 98 +/- 2% vs NL 98 +/- 4%), whereas expression levels of both COUP-TFs (COU P-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-pr oducing adenomas (DOC, n = 2), on the other hand, CYP17 expression was extr emely reduced (8 and 12% vs NL 98 +/- 4%), whereas DAX-1 expression increas ed 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 e xpression 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 receptor s play an important role in the regulation of steroidogenesis in human adre nals. (C) 2001 Academic Press.