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Chicken Ovalbumin Upstream Promoter Transcription Factor II in the Human Adrenal Cortex and Its Disorders¹

Departments of Pathology (T.S., A.D.D., T.N., J.T., H.S.) and Molecular Biology (K.T.) and Second Department of Internal Medicine (O.M.), Tohoku University School of Medicine; and Department of Pathology (T.M.), Tohoku University Hospital, Sendai 980-8575, Japan

Address all correspondence and requests for reprints to: Takashi Suzuki, M.D., Department of Pathology, Tohoku University School of Medicine, 2–1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. E-mail: t-suzuki{at}patholo2.med.tohoku.ac.jp

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.

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