Endocrinology, Vol 105, 879-883, Copyright © 1979 by Endocrine Society

ARTICLES

Stimulation of guanosine 3',5'-monophosphate-phosphodiesterase activity by adrenocorticotropic hormone-activated increase of guanosine 3',5'- monophosphate in isolated adrenocortical carcinoma cells

JP Perchellet and RK Sharma

The decline of the ACTH-stimulated cGMP to the basal level in isolated adrenocortical carcinoma cells was inhibited by cyclic phosphodiesterase inhibitors. Time-course experiments showed that the ACTH-induced level of cGMP preceded the activation of phosphodiesterase. Cells incubated with increasing concentrations of exogenous cGMP responded with a corresponding increase in the cGMP- phosphodiesterase activity. cAMP was 100-fold less effective than cGMP in the activation of cGMP-phosphodiesterase, indicating the nucleotide specificity of enzyme activation. The activation of cGMP- phosphodiesterase by ACTH-induced cGMP or exogenous cGMP was rapid. In contrast to these observations, there was no activation of cAMP- phosphodiesterase by exogenous cAMP or cGMP. These results indicate that one mechanism by which isolated adrenocortical carcinoma cells regulate the ACTH-induced increase in cGMP is the cyclic nucleotide control of the activity of its phosphodiesterase, thereby regulating cGMP degradation.