Dexamethasone at concentrations of 1.5 × 10-8 M and higher inhibited the incorporation of [14C]-proline into proline and hydroxyproline-containing protein fractions of freshly-isolated bone cells. Amino acid incorporation was only partially blocked by 1.5 × 10-8 M dexamethasone after a 5 h incubation, although incorporation could be completely blocked with puromycin. Parathyroid hormone enhanced [14C]-proline incorporation into total protein after a 3 h incubation, an effect which was abolished by simultaneous treatment with dexamethasone. Other steroids and vitamin A were tested alone and in combination with dexamethasone to determine whether the effects of these agents on bone cell protein synthesis reflected their affinities for bone cytosol binding sites previously demonstrated. At the concentrations tested, progesterone, the spirolactone SC-26304 and vitamin A all inhibited incorporation; cortexolone and estradiol did not. Cortexolone, progesterone and SC-26304 reversed the inhibitory effects of dexamethasone. These results are consistent with the earlier binding studies, and suggest that the effects of glucocorticoids on bone cell protein synthesis are mediated by cytosol receptors.
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