Ultrastructural and biochemical alterations produced in rat adrenal cortex by 4-aminopyrazolopyrimidine

The ultrastructural and biochemical changes produced by 4-aminopyrazolo[3,4-d]pyrimidine (4-APP), on zona fasciculata cells of rat adrenal cortex are described. Male rats weighing approximately 200 g were injected intraperitoneally with 50 mg/kg/day of 4-APP for 3 days; the controls were injected with buffer. All animals were sacrificed on the 4th day and the adrenals from some of them were processed for electron microscopy. The adrenals from the remaining rats were used for measurements of gland cholesterol and corticosterone; the latter was also measured in the blood. In 4-APP-treated rats the zona fasciculata cells exhibited an increase in the amount of smooth endoplasmic reticulum and in the number of free ribosomes, often arranged in polyribosomes, and a decrease in the number of lipid droplets. The nucleus showed scarce condensed chromatin and nucleolar fragmentation. The quantitative analysis showed a significant increase of the volumetric density of endoplasmic reticulum and a significant decrease of the lipid droplets in treated rats when compared with controls. Concerning the nucleus, the volumetric density of condensed chromatin significantly decreased, while the relative volume of fibrillar centers, and of granular and vacuolar components increased. In treated rats, the adrenal cholesterol and corticosterone concentrations and the blood corticosterone level were significantly decreased. These data show that 4-APP has a remarkable effect on corticosteroidogenesis and depletes the pool of adrenal cholesteryl esters, and these data stress the importance of plasma cholesterol in the steroidogenesis; on the other hand the drug appears to have a direct effect on the nucleus.