Phenobarbital-induced alterations of the rat adrenal cortex.

To determine the morpholic changes in adrenocortices induced by chronic phenobarbital therapy, the male rats were orally administered the drug daily for varying periods up to three months. Fine structural changes attributable to the drug included mitochrondrial pleomorphism and cavitation, loss of cholesterol ester clefts, reorganization of intracellular lipid, hypertrophy of the agranular endoplasmic reticulum and a juxtapositioning of the agranular endoplasmic reticulum, mitochondria and lipid droplets--all suggestive of an actively secreting cortex. The digitonin-glutaraldehyde reaction suggested an active translocation of free cholesterol from lipid droplets to the mitochondria and agranular endoplasmic reticulum following phenobarbital treatment. Phenobarbital appears to stimulate corticosteroidogenesis due in large part to enhanced hepatic corticoid metabolizing enzymes.

Fine structural and biochemical effects of aminoglutethimide and o,p'-DDD on rat adrenocortical carcinoma 494 and adrenals.

Rats bearing adrenocortical carcinoma 494 were injected daily for 7, 14, or 21 days with aminoglutethimide (AG) or o,p'-DDD. Reversibility of these steroidogenic inhibitors was determined by injecting other animals for either 14 or 21 days and sacrificing them 14 days later. While the drugs had little effect on body or tumor growth, plasma corticosterone levels were reduced a maximum of 88% in normal and 95% in tumor-bearing rats during AG chemotherapy. These levels were unaltered in normal rats by o,p'-DDD and reduced a maximum of 64% in tumor-bearing animals. Relative adrenal weights generally increased during chemotherapy and then returned to control levels. These changes were mainly due to alterations in the lipid and mitochondrial volume fractions. Lipid increased with both drugs while mitochondria increased with o,p'-DDD and decreased with AG. Cholesterol ester levels paralleled the lipid stereology more closely with AG than o,p'-DDD. With both drugs the most notable changes in tumor fine structure was a decrease in mitochondrial internal membranous vesicles and matrical density. Adrenal mitochondria had the irregular, elongated forms characteristic of tumor-bearing animals and were vacuolated (AG) or had internal rings (o,p'-DDD). The large lipid droplets observed during chemotherapy with both drugs were replaced by numerous small droplets in recovery periods.