DAX-1 expression in human adrenocortical neoplasms: implications for steroidogenesis.
The DAX-1 gene encodes an orphan nuclear hormone receptor essential for normal fetal development of the adrenal cortex. Recently, DAX-1 has been shown to act as a transcriptional repressor of steroidogenic acute regulatory protein gene expression (StAR), suppressing steroidogenesis. We, therefore, investigated the expression of DAX-1 in a variety of adrenocortical tumors and compared the results with StAR mRNA expression. We found low or absent DAX-1 expression in aldosterone-producing adenomas (n = 11: 35 +/- 11%; normal adrenals: 100 +/- 17%) and in aldosterone-producing adrenocortical carcinomas (n = 2: 24 and 36%). Cortisol-producing adenomas showed intermediate DAX-1 expression (n = 8; 92 +/- 16), as did 3 non-aldosterone-producing carcinomas (72, 132 and 132%). High DAX-1 expression was present in nonfunctional adenomas (n = 3; 160 +/- 17%). In contrast to DAX-1, StAR mRNA expression did not show significant variations between groups. We did not detect the expected negative correlation between DAX-1 and StAR in adrenocortical tumors. These data suggest that high DAX-1 expression in adrenocortical tumors is associated with a non-functional phenotype whereas low DAX-1 expression favors mineralocorticoid secretion. These effects on steroidogenesis are mediated by mechanisms other than repression of StAR gene expression. Our results indicate that DAX-1 may be one of the factors influencing the steroid biosynthesis of adrenocortical neoplasms.
Reincke
M
M
Department of Medicine II, University of Freiburg, FRG.
Beuschlein
F
F
Lalli
E
E
Arlt
W
W
Vay
S
S
Sassone-Corsi
P
P
Allolio
B
B
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000306:Adrenal Cortex Neoplasms / Q000235:genetics*; D018246:Adrenocortical Adenoma / Q000235:genetics; D018268:Adrenocortical Carcinoma / Q000235:genetics; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D012097:Repressor Proteins; D013256:Steroids / Q000096:biosynthesis*; D014157:Transcription Factors / Q000235:genetics*
D000305:Adrenal Cortex Hormones; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; C539965:NR0B1 protein, human; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D013256:Steroids; D014157:Transcription Factors