Influence of Cortisol and Insulin onin VitroIncorporation of Amino Acids Into Protein of Granuloma Tissue

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Abstract
The concept that corticoids inhibit protein anabolism at the cellular level was examined using granuloma tissue, a hormone-responsive preparation containing components of connective tissue in a stage of rapid formation. Cortisol was given at various dose levels for periods from 1 to 6 days to adrenalectomized rats bearing implants of cotton as the stimulus for granuloma formation. The resulting granulomas were incubated in Krebs-Ringer bicarbonate or rat plasma in the presence of 14C-labeled amino acids (proline, tryptophan, glycine), and the extent of amino acid incorporation into protein was determined. Although cortisol, in vivo, reduces the total protein and DNA content of this tissue, no inhibitory effect of cortisol on amino acid incorporation into protein is seen in the majority of experiments. Histological examination showed that, as the duration and amount of cortisol treatment of granulomabearing rats is increased, a progressive inhibition is observed in the normal sequences of fibroblastic and vascular proliferation and neutrophilic invasion. These effects are very marked when 5 mg/day is given for 6 days, but not histologically detectable after 1 day of cortisol treatment (4.8 mg), which is the course of treatment considered of primary interest in regard to amino acid incorporation. The evidence suggests that amino acid incorporation by the cells present in the tissue is not inhibited by cortisol, but that, at dosages sufficient to reduce cell numbers radically in vivo, an inhibition in total incorporation may appear in the subsequent in vitro situation. Insulin, added in vitro, stimulated proline incorporation into protein of granuloma from adrenalectomized or insulin-deficient rats. Prior treatment of granuloma donors with cortisol appeared to reduce this response to insulin. (Endocrinology75: 341, 1964)

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