Effects of actinomycin D, cycloheximide and puromycin on thyroid stimulation

Abstract

The administration to mice of actinomycin D, cycloheximide or puromycin was found to inhibit the influence of injected thyrotropin in stimulating in vivo the release of thyroid radioiodine. A time lapse of 8 or more hours was required for this inhibitory effect; a similar time was required for the inhibition by actinomycin D of the iodine-releasing action of the long-acting thyroid stimulator. With shorter time intervals there was no inhibition of thyrotropin or the long-acting thyroid stimulator. Major inhibition of incorporation of labeled precursor into protein was found 2 hr after injection of cycloheximide but this was much less evident after 6 hr. Actinomycin D inhibited thyroid incorporation of ³H-uridine into RNA by 21 to 46% when measurement was made in vitro with glands removed 1, 5, 9 and 24 hr after in vivo administration of the antibiotic. While it was concluded that new protein synthesis was not essential for the acute effect of thyrotropin on the release of thyroid hormone, no interpretation of the late inhibitory effects of actinomycin D on the action of thyrotropin and the long-acting thyroid stimulator seemed warranted. The 12 hr thyroid uptake of ¹³¹I in mice was enhanced by the injection of 8 μ g actinomycin D 1-24 hr before the ¹³¹I; the enhancement was additive to an increase in uptake effected by the single injection of 5 mU thyrotropin. Cycloheximide (0.5 mg injected 1-24 hr before ¹³¹I) reduced the basal thyroid uptake of ¹³¹I only when given 1 hr before the radioisotope but did not influence, with other time intervals, the thyrotropin-induced stimulation of uptake.