The effect of isomers of DDD on the ACTH-induced steroid output, histology and ultrastructure of the dog adrenal cortex

Abstract

The effect of 3 geometric isomers of DDD on ACTH-induced steroid production, histology, and ultrastructure of the dog adrenal cortex were examined. When administered iv, equal doses of all 3 compounds eventually inhibited ACTH-induced steroid production. The order of onset of inhibition was m, p′-DDD > o, p′-DDD > p, p′-DDD with the inhibition reaching 50% of control values at 27 min, 87 min and between 4–18 hr, respectively. Histologic examination of the various zones of the adrenal cortex showed minimal effects, from any of the isomers, on the zona glomerulosa at times when the internal structure and spacial arrangement of the cells of the zona fasciculata and reticularis were markedly disrupted. Electron micrographs revealed that these DDD isomers exhibited very minimal effects on the mitochondria of the zona glomerulosa. On the other hand, the mitochondria of the zonas fasciculata-reticularis underwent progressive swelling, dissolution, and eventual rupture following DDD treatment. The order of onset of histologic and ultrastructural effects was m, p′-DDD > o, p′-DDD > p, p′-DDD. However, for each isomer the ultrastructural damage was detected prior to the observation of histologic lesions. Thus, there was a marked temporal correlation between the percentage inhibition of ACTH-induced steroid production, the disruption of normal cellular structure and arrangement in the innermost zones of the adrenal cortex, and the severity of the DDD-induced mitochondria damage in the cells of the zonas fasciculata-reticularis by each of the 3 isomers of DDD.