title: Orphan receptors COUP-TF and DAX-1 as targets in disordered CYP17 expression in adrenocortical tumors.
abstract: 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.
authors.affiliation: Health Center and Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. hiro-405@cb3.so-net.ne.jp
authors.forename: H
authors.initials: H
authors.lastname: Shibata
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeda
authors.forename: K
authors.initials: K
authors.lastname: Morohashi
authors.forename: T
authors.initials: T
authors.lastname: Mukai
authors.forename: I
authors.initials: I
authors.lastname: Kurihara
authors.forename: T
authors.initials: T
authors.lastname: Ando
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.forename: M
authors.initials: M
authors.lastname: Hayashi
authors.forename: I
authors.initials: I
authors.lastname: Saito
authors.forename: T
authors.initials: T
authors.lastname: Saruta
mesh_terms: 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
chemical_list: 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