Long term effects of the hypocholesterolaemic drug 4-aminopyrazolo-pyrimidine on the zona fasciculata of the rat adrenal cortex.

Prolonged 4-APP administration to dexamethasone/ACTH-treated rats was found to lower both plasma and intra-adrenal gland cholesterol concentrations. Morphological examination showed that zona fasciculata cells underwent a severe lipid droplet depletion, and a conspicuous increase of agranular endoplasmic reticulum and peroxisomes. The blood level of corticosterone remained unchanged. A high cholesterol diet completely reversed the effects of 4-APP treatment. The hypothesis is discussed that these morphological changes are the expression of a compensatory response enabling rat adrenocortical cells to maintain an adequate level of hormone output even in the absence of a normal supply of exogenous cholesterol.