Orphan receptors COUP-TF and DAX-1 as targets in disordered CYP17 expression in adrenocortical tumors.
CYP17 gene transcription is activated by SF-1 binding to a cyclic AMP-responsive sequence within the promoter region of the gene, and its transcription is inhibited by COUP-TF binding to the sequence. Another orphan receptor, DAX-1, is shown to act as a suppressor of SF-1-mediated transcription. We examined the expression level of these orphan receptors in adrenocortical tumors and compared the results with CYP17 expression. CYP17 was highly expressed in cortisol-producing adenomas, whereas COUP-TF and DAX-1 expression levels were very low. In deoxycorticosterone-producing adenomas, on the other hand, CYP17 expression was extremely low, whereas DAX-1 was highly expressed and SF-1 expression was slightly decreased. In conclusion, the reciprocal expression of CYP17 and the transcriptional repressors COUP-TF and DAX-1 indicates that these orphan receptors have a pathophysiologic role in the excessive hormone production in cortisol- and deoxycorticosterone-producing adrenocortical tumors.
Shibata
H
H
Health Center and Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. hiro-405@cb3.so-net.ne.jp
Ikeda
Y
Y
Morohashi
K
K
Mukai
T
T
Kurihara
I
I
Ando
T
T
Suzuki
T
T
Kobayashi
S
S
Hayashi
K
K
Hayashi
M
M
Saito
I
I
Saruta
T
T
D000306:Adrenal Cortex Neoplasms / Q000235:genetics*; D051836:COUP Transcription Factors; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051717:Fushi Tarazu Transcription Factors; D015870:Gene Expression / Q000502:physiology*; D018398:Homeodomain Proteins; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid / Q000235:genetics* / Q000378:metabolism; D011987:Receptors, Steroid; D012097:Repressor Proteins; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics* / Q000378:metabolism; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D051836:COUP Transcription Factors; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; C539965:NR0B1 protein, human; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011987:Receptors, Steroid; D012097:Repressor Proteins; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D013254:Steroid 17-alpha-Hydroxylase