Uncoupling by cooling of secretion and adenosine 3',5'-monophosphate accumulation in stimulated dog thyroid slices

Thyroid metabolism undergoes general activation in the presence of TSH. Secretion, [1-14C]-glucose oxidation, protein iodination, and cyclic AMP (cAMP) accumulation are stimulated. In intact tissue, it is difficult to dissociate effects of cAMP itself and effects secondary to cAMP-induced secretion. We report herein that cooling to 20 C dissociates the action of TSH on secretion from all its other effects. At this temperature, TSH stimulation of secretion was completely inhibited whereas cAMP accumulation was enhanced. The TSH effect on [1-14C]glucose oxidation was maintained and its action on protein iodination was diminished but not abolished. The ATP content was not decreased. The mechanism of action of cooling was investigated. No pseudopod formation of intracellular colloid droplets were observed by scanning electron microscopy and transmission electron microscopy, thus indicating that the inhibition affects the first step of secretion, i.e., colloid phagocytosis. Microtubules were not seen at 2 C but were normally present at 20 C. The data are compatible with the hypothesis that inhibition of phagocytosis at 20 C could be a consequence of a lipid phase transition in the membrane.