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Although actinomycin D has been used to prevent protein synthesis in experiments of several hours' duration, its effects on the synthesis of adaptive enzymes which are induced over a period of several days have received less attention. Treatment of young rats with doses of actinomycin D, which permitted survival for a period of 5 days, resulted in marked increases in the activities of four hepatic enzymes known to be induced by cortisol: alanine transaminase, tyrosine transaminase, serine dehydrase, and tryptophan pyrrolase. Actinomycin D also induced responses of two of these enzymes in adrenalectomized rats.

In vitro antiglucocorticoids (cortexolone and progesterone) were evaluated as in vivo antagonists of dexamethasone-induced increases in liver tyrosine amino transferase (TAT; EC 2.6.1.5), tryptophan oxygenase (TPO; EC 1.13.1.12), and glycogen deposition. Cortexolone antagonized the TPO and glycogen responses to dexamethasone in the liver of adrenalectomized rats but did not significantly influence the induced TAT activity. Progesterone, although toxic at levels approaching those used for cortexolone, was capable of antagonizing the glycogen increase. A new antagonist, 6 beta-bromoprogesterone, was found to be nontoxic and was more potent than cortexolone in blocking the TPO and glycogen responses. These results demonstrate that in vivo antiglucocorticoid activity can be evaluated and suggested significant differences between the sensitivity of TAT induction and that of glycogen or TPO.

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