Stereologic studies on the adrenal cortex of 4-APP (4-amino-pyrazolopyrimidine)-induced lipoprotein-deficient rats

The effect of 4-APP (4-aminopyrazolopyrimidine), the compound reducing hepatic release of lipoproteins, on the rat adrenal cortex was studied by means of stereological methods. Within 3 days 4-APP resulted in a marked increase in the absolute and relative adrenal weights and markedly lowered plasma and adrenal total cholesterol concentration. 4-APP did not change the relative volume of individual adrenocortical zones, however significantly increased the volume in mm3 of the zona fasciculata (ZF) and reticularis (ZR) and of the entire cortex. The average volume of the ZF and ZR cells of 4-APP treated rats was markedly higher than in control rats while no difference was found in the zona glomerulosa (ZG) cell. In lipoprotein-deficient rats the number of adrenocortical cells within the entire cortex was similar to that observed in control rats. A marked increase in the number of mitoses in both, adrenocortical and endothelial cells suggests inhibitory action of 4-APP on the proliferative activity of these cells. The present study shows that 4-APP-induced changes in the rat adrenal cortex mainly depends upon the stimulatory action of that compound on ACTH secretion, however this adenine analogue also exerts a direct action on the adrenocortical cells.