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.
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