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Abstract

Tissue cultures of fetal rat adrenals were used to study effects of cycloheximide on the ACTH-induced synthesis of mitochondrial inner membranes in the cortical cells. Cycloheximide alone added to the culture medium in concentrations of 100-0.25 μg/ml killed the cortical cells during six days of treatment. At the dosage level of 0.15 μg/ml/6 days, it induced a decrease in the size of mitochondria and an increase in the pleomorphism of mitochondria. Cycloheximide at a concentration of 0.015 μg/ml/6 days induced no change in the ultrastructure of cortical cells. When cycloheximide in concentrations of 0.15 μg/ml/6 days was added to the culture medium together with 100 mU/ml/6 days of ACTH, the ACTH-induced changes of mitochondrial inner membranes (formation of 600 Å vesicles) was completely inhibited. It also suppressed the ACTH-induced development of smooth surfaced endoplasmic reticulum, hypertrophy of Golgi apparatus, development of microvilli and accumulation of lipids. However, it had no effects on the ACTH-induced increase in the number of polysomes 01 the increase of heterochromatin in the nucleus. Cycloheximide (0.08 μg/ml/6 days) given together with 100 mU/ml/6 days of ACTH had incomplete inhibitory effects on the ACTH-induced differentiation of the cortical cells. Cycloheximide (0.015 μg/ml/6 days) given together with ACTH resulted in only slight inhibition of ACTH-induced ultrastructural differentiation of adrenal cortical cells in vitro.

The present observations suggest that (1) the stimulatory effect of ACTH on mitochondrial protein synthesis is dependent upon nuclear control of protein synthesis; (2) a specific cytoplasmic mitochondrial protein synthesis stimulating factor in the cytoplasm of cortical cells is dependent on ribosomal protein synthesis and is a mediator of ACTH action on the mitochondrion; (3) despite their apparent autonomy, the mitochondria in cortical cells are kept under nuclear control; (4) the only direct locus for the trophic effect of ACTH is in the nucleus.