Chicken ovalbumin upstream promoter transcription factor II in the human adrenal cortex and its disorders.
Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an orphan member of the steroid/thyroid hormone receptor superfamily. COUP-TFII has been demonstrated to negatively regulate the transcriptional activity of adrenal 4-binding protein, a steroidogenic cell-specific transcription factor that activates the transcription of various steroidogenic P450 genes. We therefore examined immunolocalization of COUP-TFII in the human adrenal cortex and its disorders, including functioning and nonfunctioning cortical tumors, to study its possible correlation with adrenocortical steroidogenesis. In nonpathological adrenal cortex, COUP-TFII immunoreactivity was marked in the nuclei of adrenocortical cells in definitive and fetal zones from 16 gestational weeks to 2 months after birth. Immunoreactivity for COUP-TFII was marked in the zona glomerulosa and weak in the zonae fasciculata and reticularis from 7 months to 8 yr of age, but thereafter markedly decreased in these zones (P < 0.05, between age 7 months to 8 yr and 24-62 yr of age, respectively). In adrenocortical tumors, COUP-TFII immunoreactivity was marked in the nuclei of tumor cells of aldosteroma (H score, 134 +/- 15.9; P < 0.001 vs. Cushing's adenoma and P < 0.05 vs. nonfunctioning adenoma and carcinoma), modest in nonfunctioning adenoma (82.7 +/- 19.8) and adrenocortical carcinoma (79.6 +/- 56.3), and low in Cushing's adenoma (38.2 +/- 24.5). Results from immunoblotting performed in seven cases of adenomas were consistent with those of immunohistochemistry. In the attached nonneoplastic adrenal cortex of the adenomas, immunoreactivity for COUP-TFII was markedly increased compared to that in nonpathological adrenal cortex in adults and was especially marked in the zona glomerulosa in the attached adrenal of aldosteroma (P < 0.001) and the zona fasciculata in that of Cushing's adenoma (P < 0.05). COUP-TFII immunoreactivity was universally detected in stromal cells of the adrenal glands. These results suggest that COUP-TFII plays an important role in the regulation of steroidogenesis in human adrenal cortex and its disorders.
Suzuki
T
T
Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
Takahashi
K
K
Darnel
A D
AD
MoriyaT
Murakami
O
O
Narasaka
T
T
Takeyama
J
J
Sasano
H
H
D000236:Adenoma / Q000473:pathology*; D000293:Adolescent; D000302:Adrenal Cortex / Q000166:cytology / Q000196:embryology* / Q000254:growth & development*; D000306:Adrenal Cortex Neoplasms / Q000473:pathology*; D000328:Adult; D000375:Aging; D051837:COUP Transcription Factor II; D051836:COUP Transcription Factors; D002648:Child; D002675:Child, Preschool; D003480:Cushing Syndrome / Q000473:pathology; D004268:DNA-Binding Proteins / Q000032:analysis*; D005333:Fetus; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D011987:Receptors, Steroid / Q000032:analysis; D014157:Transcription Factors / Q000032:analysis*
D051837:COUP Transcription Factor II; D051836:COUP Transcription Factors; D004268:DNA-Binding Proteins; D011987:Receptors, Steroid; D014157:Transcription Factors; C095569:NR2F2 protein, human