Stimulation in vitro by thyrotropin, cyclic 3′,5′-AMP, dibutyryl cyclic 3′,5′-AMP and prostaglandin E 1, of secretion by dog thyroid slices

Abstract

The release of 131I radioactivity extracted by butanol (thyroid hormones and iodide) in vitro from slices of prelabeled thyroids removed from pretreated dogs is measured. Results are compared with measurements of intracellular colloid droplet formation. Several arguments support the hypothesis that the in vitro release corresponds to secretion. Secretion in vitro was apparently delayed. Secretion in vitro as well as intracellular colloid droplet formation was enhanced by thyroid stimulating hormone (TSH), cyclic AMP (cAMP), N 6-2- O-dibutyryl cyclic AMP (b 2cAMP), and prostaglandin E 1, but not by caffeine, AMP or ATP. The kinetics of these effects were similar for the 4 stimulating agents. Concentration effect relationships for the 4 compounds are presented. Orders of magnitude of equieffective concentrations were TSH 0.25 mU/ml, cAMP 3.5–10 mM, b 2cAMP 0.1 mM. The concentration effect curve of prostaglandin E 1 was biphasic. The results support the hypothesis that the induction by TSH of thyroid secretion is mediated by cAMP. For low concentrations of TSH intracellular colloid droplet formation varied greatly from cell to cell, thus suggesting a marked intercellular functional heterogeneity. Several facts suggest that in the in vitro system thyroglobulinolysis may become the limiting step of secretion at high levels of thyroid stimulation.