Ca<SUP>2+</SUP>-Dependency of Phosphodiesterase Activities in Normal and Pathological Human Thyroids

Abstract

It has been reported that cyclic nucleotide phosphodiesterase (PDE) has multiple forms, and one of them is activated by PDE-activating factor (PAF) in many tissues. Also it has been suggested that PAF plays an important role in the control of intracellular cyclic nucleotide concentrations. But PDE and PAF have not been studied sufficiently in the human thyroid. We report in this article the occurrence of multiple forms and of an activating factor of PDE in the human thyroid. We also report how the PDE activities and their properties in thyroids with various diseases differ from those in the normal thyroid.The PDE activities for cyclic AMP and for cyclic GMP in the 100,000 × g supernatant of the human thyroid were activated by Ca2+ in the presence of Mg2+. Sephadex G-200 gel-filtration profiles of the activities of the supernatant revealed three peaks of cyclic AMP PDE activity, three peaks of cyclic GMP PDE activity and one peak of PAF activity. The second peaks of cyclic AMP and cyclic GMP PDE activities were eluted at the same position and were activated by PAF in the presence of Ca2+. The fact that the enzyme activities of other peaks were not influenced by Ca2+ indicated that Ca2+-dependency in the supernatant was due to the presence of the PAF-dependent PDE form. This activating system of PDE may have a role in the control of intracellular cyclic nucleotide concentrations in the human thyroid. The molecular weights of the PAF-dependent PDE form and PAF were estimated to be 145,000 and 26,000, respectively.The PDE activities per gram of tissue for cyclic AMP and for cyclic GMP of the 100,000 × g supernatants of Graves' thyroid, thyroid adenoma and carcinoma were increased as compared with the normal thyroid. It could not be clarified whether or not this increase was merely due to cellular hypertrophy For an increase in cell population density. The ratios of cyclic GMP PDE activity to cyclic AMP PDE activity were increased in Graves' thyroid and thyroid carcinoma. Ca2+-Dependency of the PDE activity was increased in thyroid carcinoma when cyclic AMP was used as a substrate, and in Graves' thyroid and thyroid adenoma when cyclic GMP was used. These changes of the PDE activities suggest abnormality of cyclic nucleotide metabolism in the thyroids of patients with these diseases. Hydrolysis of cyclic AMP in Graves' thyroid may be influenced by altered PDE activity.