An Anomalous Effect of Theophylline on ACTH and Adenosine 3′,5′-Monophosphate Stimulation.

Summary The action of several peptide and amine hormones on their target tissues involves the generation of adenosine-3′-5′-monophosphate (3′5′-AMP). Inhibition of the enzymatic breakdown of 3′5′-AMP by high concentrations of theophylline results, in most of these hormone-tissue systems, in a simulation of the hormone effect or in a po-tentiation of its action. Adrenocorticotrophin (ACTH) action on steroidogenesis in adrenals, which involves 3′,5′-AMP formation; is not affected by theophylline to the same degree as the actions of other hormones on their target tissues. A possible explanation for this discrepancy may be found in the fact that high concentrations of theophylline inhibit protein synthesis in surviving rat adrenal tissue, a process which is known to be involved in the steroidogenic action of both ACTH and 3′,5′-AMP. It is suggested that theophylline action in rat adrenals has two antagonistic components, (1) potentiation of the steroidogenic action by protection of .3′,5′-AMP, and (2) reduction of the steroidogenic action by inhibition of protein synthesis.