DAX-1 EXPRESSION IN HUMAN ADRENOCORTICAL NEOPLASMS - IMPLICATIONS FORSTEROIDOGENESIS

The DAX-1 gene encodes an orphan nuclear hormone receptor essential fo r normal fetal development of the adrenal cortex Recently, DAX-1 has b een shown to act as a transcriptional repressor of steroidogenic acute regulatory protein gene expression (StAR), suppressing steroidogenesi s. We, therefore, investigated the expression of DAX-1 in a variety of adrenocortical tumors and compared the results with StAR mRNA express ion. We found low or absent DAX-1 expression in aldosterone-producing adenomas (n=11: 35+/-11%; normal adrenals: 100+/-17%) and in aldostero ne-producing adrenocortical carcinomas (n=2: 24 and 36 %). Cortisol-pr oducing adenomas showed intermediate DAX-1 expression (n=8; 92+/-16), as did 3 non-aldosterone-producing carcinomas (72, 132 and 132 %). Hig h DAX-1 expression was present in nonfunctional adenomas (n=3; 160+/-1 7%). In contrast to DAX-1, StAR mRNA expression did not show significa nt variations between groups. We did not detect the expected negative correlation between DAX-1 and StAR mRNA in adrenocortical tumors. Thes e data suggest that high DAX-1 expression in adrenocortical tumors is associated with a non-functional phenotype whereas low DAX-1 expressio n favors mineralocorticoid secretion These effects on steroidogenesis are mediated by mechanisms other than repression of StAR gene expressi on. Our results indicate that DAX-1 may be one of the factors influenc ing the steroid biosynthesis of adrenocortical neoplasms.