Stimulatory actions of thyrotropin and dibutyryl cyclic AMP on transcription and translation in the regulation of thyroidal protein synthesis

Abstract

When beef thyroid cells were incubated with thyrotropin and then tested for protein synthesizing activity, the stimulatory effect of thyrotropin appeared in two distinct phases: first, an immediate stimulation which continued as long as thyrotropin was present, but died away promptly after withdrawal of the added thyrotropin; and second, a delayed stimulation with a lag period of 1 to 2 h, which persisted after thyrotropin withdrawal. The fast and the delayed effects each stimulated protein synthesis by about 25%, so that after 4 h of thyrotropin treatment, total stimulation amounted to 50% above basal levels of activity. The fast thyrotropin effect was not affected by actinomycin D or cordycepin, and hence is evidently not dependent upon induced RNA synthesis. In contrast, the delayed thyrotropin effect was completely prevented by actinomycin D or cordycepin. These findings suggest that the fast effect of thyrotropin occurs at the translational level to provide for acute adjustments in thyroglobulin production by regulating the rate of translation of existing mRNA. The delayed thyrotropin effect, by initiating certain transcriptional reactions could be the means for selectively inducing the production of specific enzymes or proteins. Both the fast and delayed effects of thyrotropin were faithfully reproduced by dibutyryl cyclic AMP. This finding seems to be the first in vitro demonstration of a cyclic AMP induced transcriptional response to a hormone in mammalian cells.