ITOH, GEN

Aminoglutethimide (Elipten, Ciba,) interferes with the biosynthesis of adrenocortical hormones by blocking the conversion of cholesterol to pregnenolone. Male albino rats were fed with the diet containing aminoglutethimide and were killed after various time intervals ranging from 24 hours to 7 days. The adrenal cortices of these animals were studied both by light and electron microscopy. Special effort was made to determine the intracellular localization of free cholesterol by an electron microscopic histochemical method using the digitonin reaction. The animals killed 24 hours after the initiation of the feeding were found to have small myelin figures in contact with the mitochondrial membrane in fasciculata cells which might reflect compensatory rise of ACTH. The animals fed with the diet for 4 to 7 days were shown to have enlarged adrenal cortex. Light microscopic examination revealed an increase of the lipid globules both in size and number in the zona fasciculata. Ultrastructural studies showed swollen, hypertrophied, bizarre prophiles of the mitochondria with the formation of the vacuoles. The electron microscopic histochemical method demonstrated digitonincholesterol crystals localized in the vacuoles of the mitochondria, in the perimitochondrial areas and in the lipid globules. These findings correlate well with the biochemical data which indicate the intracellular site of steroid bicsynthesis and lend morphological support to the view that the biosynthesis of pregnenolone from cholesterol takes place within the mitochondria. These results indicate that aminoglutethimide causes accumulation of cholesterol in the vacuoles of the mitochondria

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Electron Microscopic Studies on the Adrenal of Rat Treated with Aminoglutethimide : With Special Reference to Accumulation of Cholesterol in Intramitochondrial Vacuoles

Electron Microscopic Studies on the Adrenal of Rat Treated with Aminoglutethimide : With Special Reference to Accumulation of Cholesterol in Intramitochondrial Vacuoles

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