Effect of Lysodren(R) on the Ultrastructural Changes in the Rat Adrenal Corex: Immunohistochemical staining for anti-ACTH antibody on the adenohypophysis

ABSTRACT

The toxicity and adrenostatic effect of o,p'-DDD, a derivative of the insecticidal DDT, on the adrenal cortex were well known. It known that the toxicity was based on the blocking of steroid biopsynthesis when cholesterol was converted to pregnenolone. Lysodren(R) was also known to be capable of producing a regression of adrenocortical carcinoma and its metastases, and this drug became one of useful choice for the treatment of unoperable adrenocortical carcinomas. Recently, fine structural effect of o,p'-DDD on the adrenocortical carcinoma show that the mitochondria is the primary target organelle. o,p'-DDD was dissolved in corn oil and it was orally administered for 28 days to investigate the ultrastructural effects of zona fasciculata of rat adrenal cortex. The results obtained were as follow 1) The body weight was decreased after feeding o,p'-DDD. 2) Light microscopic examination showed no remarkable change except increased fine lipid droplets of zona fasciculata in group I (o,p'-DDD 75 mg/kg feeding). Moderately increased intracytoplasmic lipid droplets and pyknotic nuclei bearing membrane indentations were seen in group II (o,p'-DDD 150 mg/kg feeding). Large sized lipid droplet aggregates, pyknotic nuclei with severe nuclear membrane indentations and karyorrhexis in focal area were evident in group III. 3) Immunohistochemical staining for ACTH in pituitary gland showed increasing number of ACTH secretory cell and increasing intensity of staining property according to the dosage of o,p'-DDD. 4) Ultrastructural examination showed increased intracytoplasmic lipid droplets and mild increased peroxisome. There was no remarkable ultrastructural changes in mitochondria in group I. Moderately increased lipid droplets and clusters formation, compressed mitochondria, partial disappearance of mitochondrial cristae, increased peroxisome and nuclear membrane indentations were seen in group II. In group III, nuclear membrane showed prominent indentation. Numberous cytoplasmic vacuolation, double membrane ring in mitochondria, disappearance of mitochondrial cristae, myelin figure formation in mitochondrial matrix, and fatty changes in mitochondrial matrix were seen. These findings showed that the primary target organelle of attack by o,p'-DDD on zona fasciculata of adrenal gland in rat is mitochondria and it was developed from double ring formation in mitochondrial matrix.