Nuclear receptors in the pathophysiology of endocrine tumors
Shibata, H.
Nihon Rinsho. Japanese Journal of Clinical Medicine 60(2): 237-244
2002
ISSN/ISBN: 0047-1852 PMID: 11857908 Document Number: 544896
Nuclear orphan receptors COUP-TF and DAX-1 negatively regulate the transcriptional activity of SF-1, a steroidogenic cell-specific activator of various steroidogenic cytochrome P-450 genes. Expression of COUP-TF and DAX-1 are greatly decreased in cortisol-producing adrenocortical adenomas, while CYP17 is overexpressed. In contrast, DAX-1 expression is increased and SF-1 expression is decreased in deoxycorticosterone-producing adrenocortical adenomas, where CYP17 expression is low. These data suggest that DAX-1 and/or COUP-TF may repress CYP17 expression in adrenocortical tumors. In addition, SF-1 is expressed in the human pituitary gonadotroph and pituitary adenomas of gonadotrophic origin. SF-1 expression is associated with the in vitro secretion of LH in pituitary adenomas. Opposing effects of SF-1 and DAX-1 and/or COUP-TF may regulate the differential responses of various SF-1 target genes in different endocrine tumors.