Effects of prolonged treatment with cyanoketone on the zona fasciculata of rat adrenal cortex. A combined morphometric and biochemical study.

The effects of a 7-day administration of cyanoketone (CKT) on the adrenal zona fasciculata were examined in "normal" and dexamethasone/ACTH-infused rats. The drug caused a 48-56% decrease in the blood concentration of corticosterone, coupled with a 53-58% lowering in the activity of 3 beta-hydroxysteroid dehydrogenase (3 beta HSD), in both groups of animals. In the "normal" rats, CKT induced a significant hypertrophy of the zona fasciculata and its parenchymal cells, due to an increase in volume of the mitochondrial compartment and to proliferation of the smooth endoplasmic reticulum (SER), as well as a notable rise in both the volume of the lipid-droplet compartment and the intracellular concentration of total cholesterol. The activity of 11 beta-hydroxylase was conspicuously enhanced. All these responses of zona fasciculata cells to CKT did not occur in dexamethasone/ACTH-treated animals, and therefore they were considered to be non-specific and mediated by the augmented secretion of ACTH following lowering of the corticosterone level in the blood. In the dexamethasone/ACTH-infused rats, the only morphological change induced by CKT was a significant decrease in the surface area per cell and surface density of the SER, which was interpreted as the morphological counterpart (not masked by the increased level of circulating ACTH) of the drug-induced inhibition of the microsomal 3 beta HSD.