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Inhibition of ACTH-induced differentiation of cortical cells and their mitochondria by corticosterone in tissue culture of fetal rat adrenals
Authors:Arvi I Kahri
Abstract:Tissue cultures of fetal rat adrenals were used to study the effects of corticosterone on the ACTH-induced ultrastructural differentiation of cortical cells and their mitochondria. Corticosterone in dosages of 0.2, 2.0, 5.0, 10, and 20 μg/ml (corresponding to concentrations of 6 × 10?7, 6 × 10?6, 1.5 × 10?5, 3 × 10?5, and 6 × 10?5 molar) was added alone or together with 100 mU/ml of ACTH to the culture medium, daily from the sixteenth day of cultivation up to and including the twenty-first day. Corticosterone alone induced no ultrastructural changes in cortical cells. Corticosterone in concentrations of 6 × 10?7 to 3 × 10?5 M given with ACTH induced hypertrophy of Golgi apparatus. Corticosterone in concentrations of 6 × 10?5 M inhibited the ACTH-induced differentiation of cortical cells. However, the nuclear chromatin increased and Golgi apparatus was strikingly hypertrophied. Mitochondria often aggregated adjacent to the nuclear envelope but their ultrastructure remained undifferentiated with tubular or tubulovesicular cristae. Ribosomes appeared as single particles. A marked increase of smooth surfaced endoplasmic reticulum was noted also in cortical cells treated with 6 × 10?5 M of corticosterone. The present observations suggest that corticosterone acts as an intracellular inhibitor in cortical cells. It appears to inhibit cytoplasmic protein synthesis at the ribosomal level and prevents synthesis of cytoplasmic mitochondrial protein synthesis stimulating factor and the latter, in turn, inhibits the activation of mitochondrial protein synthesis. A new model is presented to explain the regulation of growth and secretion in the adrenal cortex.
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