Cyclic 3',5'-nucleotide phosphodiesterase activities in the thyroid glands of patients with various disorders

Thyroid tissue was found to contain at least least two separable cyclic 3',5'-nucleotide phosphodiesterase (cAMP-PDE and cGMP-PDE) activities, as determined by DEAE-cellulose or Sepharose 6B column chromatography. These activities were cAMP- and cGMP-hydrolyzing enzymes. Quantitative differences of cAMP or cGMP hydrolytic activity were observed in tissues from patients with thyroid disorders. Theophylline, modulator protein, and Mg2+ produced similar effects on cAMP or cGMP hydrolytic activity in tissues from patients with a without various thyroid disorders. The mode of the inhibitory effect of cyclic nucleotides on PDE activities in thyroid tissues was competitive, in contrast to the mode seen in other organs. Both cAMP and cGMP hydrolytic activities were elevated in the tissues from patients with hyperthyroidism and thyroid carcinoma compared with the activity in controls. cGMP hydrolysis in hyperthyroidism was 4.4-fold higher than that seen in the controls. The ratio cGMP to cAMP hydrolysis was highest in cases of hyperthyroidism and lowest in cases of thyroid carcinoma, when PDE activities were determined with a substrate concentration of 0.4 microM. Kinetic analysis revealed that higher PDE activity in tissues from patients with hyperthyroidism and thyroid carcinoma was due to an increase in maximal velocity. The apparent Km values for hydrolysis of cyclic nucleotides were similar in normal and pathological thyroid tissues.