Differential expression of a stress-modulating gene, BRE, in the adrenal gland, in adrenal neoplasia, and in abnormal adrenal tissues

Genes that modulate the action of hormones and cytokines play a critical ro le in stress response, survival, and in growth acid differentiation of cell s. Many of these biological response modifiers are responsible for various pathological conditions, including inflammation, infection, cachexia, aging , genetic disorders, and cancer. We have previously identified a new gene, BRE, that is responsive to DNA damage and retinoic acid. Using multiple-tis sue dot-blotting and Northern blotting, BRE was recently found to be strong ly expressed in adrenal cortex and medulla, in testis, and in pancreas, whe reas low expression was found in the thyroid, thymus, small intestine and s tomach. In situ hybridization and immunohistochemical staining indicated th at BRE was strongly expressed in the zona glomerulosa of the adrenal cortex , which synthesizes and secretes the mineralocorticoid hormones. It is also highly expressed in the glial and neuronal cells of the brain and in the r ound spermatids, Sertoli cells, and Ledig cells of the testis, all of which are associated with steroid hormones and/or TNF synthesis. However, BRE ex pression was downregulated in human adrenal adenoma and pheochromocytoma, w hereas its expression was enhanced in abnormal adrenal tissues of rats chro nically treated with nitrate or nitrite. These data, taken together, indica te that the expression of BRE is apparently associated with steroids and/or TNF production and the regulation of endocrine functions. BRE may play an important role in the endocrine and immune system, such as the cytokine-end ocrine interaction Of the adrenal gland.