Biochemical and ultrastructural changes in the adrenal glands of rats were observed after long-term phenobarbital treatment. At the fine structural level, the parenchymal cells of the phenobarbital-treated rats resembled cortical cells that had been stimulated by adrenocorticotropin. A significant finding was the presence of very large hollow mitochondria characterized by loss of vesicles and cristae with retention of the double outer membrane. Arylesterase (EC 3.1.1.2) activity, the marker used for rough endoplasmic reticulum, was significantly diminished. Since rough endoplasmic reticulum is present primarily in the adrenal medulla and not the cortex, the relative decrease in arylesterase activity is consistent with the morphologic adrenal cortical hyperplasia. Trypsin-like (EC 3.4.4.4) enzyme activity was increased. The plasma corticosterone response to adrenocorticotropin injection was not significantly different in treated and control rats. The similarity of the observed mitochondrial changes to the reported mitochondrial cavitation in the adrenal glands of rats treated with aminoglutethimide is discussed.
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