Superoxide Dismutase in Human Adrenal and its Disorders: A Correlation with Development and Neoplastic Changes

In adrenal glands, oxidative free radicals are synthesized in the course of hormonal production, and enzyme superoxide dismutase (SOD) is considered to scavenge these harmful superoxide radicals and, subsequently, to protect the cells. We studied immunohistochemical localization of Mn (manganese)-SOD and Cu,Zn (copper-zinc)-SOD in human adrenal and its disorders from fetus to adult obtained from autopsy or surgery in order to examine the possible biological significance of these two enzymes. In fetal adrenal (n = 4), Cu,Zn-SOD and Mn-SOD were detected only in the fetal cortex. In adrenal glands from children (n = 21) to adults (n = 15), Mn-SOD immunoreactivity was exclusively detected in adrenal medulla, whereas Cu,Zn-SOD immunoreactivity was present only in adrenocortical parenchymal cells, weakly in the zona glomerulosa, and markedly in the zona reticularis. There were no differences in relative immunointensity and/or patterns of immunolocalization of these two SODs among different age groups. Both Cu,Zn-SOD and Mn-SOD immunoreactivity were detected in compact tumor cells of adrenocortical adenoma (n = 16). Marked immunoreactivity of both Cu,Zn-SOD and Mn-SOD was detected in adrenocortical carcinoma (n = 11) and pheochromocytoma (n = 5). These results indicate that Cu,Zn-SOD and Mu-SOD may play different roles as a scavenger or antioxidants in normal human adrenal glands, i.e., Cu,Zn-SOD as a scavenger of toxic superoxide radicals generated during steroidogenesis and Mn-SOD during catecholamine production. Cu,Zn-SOD and Mn-SOD immunoreactivities detected in adrenal neoplasms are also considered to represent altered expression of these enzymes associated with neoplastic transformation, as reported in other human malignancies.