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 activ ity of adrenal 4-binding protein, a steroidogenic cell-specific transcripti on factor that activates the transcription of various steroidogenic P450 ge nes. We therefore examined immunolocalization of COUP-TFII in the human adr enal cortex and its disorders, including functioning and nonfunctioning cor tical tumors, to study its possible correlation with adrenocortical steroid ogenesis. 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 CO UP-TFII was marked in the zona glomerulosa and weak in the zonae fasciculat a and reticularis from 7 months to 8 yr of age, but thereafter markedly dec reased 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 <plus /minus> 15.9; P < 0.001 vs. Gushing's adenoma and P < 0.05 vs. nonfunctioni ng adenoma and carcinoma), modest in nonfunctioning adenoma (82.7 +/- 19.8) and adrenocortical carcinoma (79.6 +/- 56.3), and low in Gushing's adenoma (38.2 +/- 24.5). Results from immunoblotting pet-formed in seven cases of adenomas were consistent with those of immunohistochemistry. In the attache d nonneoplastic adrenal cortex of the adenomas, immunoreactivity for COUP-T FII was markedly increased compared to that in nonpathological adrenal cort ex in adults and was especially marked in the zona glomerulosa in the attac hed adrenal of aldosteroma (P < 0.001) and the zona fasciculata in that of Gushing's adenoma (P < 0.05). COUP-TFII immunoreactivity was universally de tected in stromal cells of the adrenal glands. These results suggest that C OUP-TFII plays an important role in the regulation of steroidogenesis in hu man adrenal cortex and its disorders.