Some Effects of Actinomycin D on Iodine Metabolism in the Rat Thyroido

Abstract

ActinomycinD (act D), given to intact rats in a dose of 80 [mu]g/100 g body wt 2 or 15 hr. before I131, failed to influence significantly its 4-hr, uptake by the thyroid. Sixteen hr. after act D, thyroidal organic binding of I131 (determined during the first 8 min. after its injection) was unimpaired. The thyroid-serum 1131- concentration ratio (T/S) of intact rats was substantially raised by act D injected 15-16 hr. before 1131; since the latency of this effect could be as little as 4 hr. it was apparently not due to the release of endogenous TSH [thyroid-stimulating hormone]. Depletion of thyroidal organic Iodine with propylthiouracil (PTU), followed by suppression of TSH secretion with triiodothyrontne (T3), prevented an effect of act D on the T/S when the treatment with both PTU and T3 was sufficiently intensive. The influence of act D was also abolished when rats were deprived of their source of circulating TSH (without previous stimulation of its output with PTU) by chronic T3-treatment or hypophysectomy (in all hypophy-sectomized rats, the dose of act D was 40 [mu]g/100 g). When TSH was given to hypophysectomized rats 1 hr. after act D, the enhancing effect of the former on the T/S was undiminished, or even significantly potentiated. In hypophysectomized rats treated with TSH for 3 days, act D given on the last day, 13 hr. before 1131, more than doubled the T/S over the value to which TSH alone raised it. Act D administered 1 hr. preceding TSH to intact rats, whose thyroids were prelabeled with 1131, and which also received PTU 30min. after act D, blocked the depletion of I131 caused by TSH during a 22-hr, period. In similar experiments in which 1 lobe of the thyroid was removed before TSH administration, so that each rat was its own control, act D given 1 hr. before TSH had an equivocal effect on the TSH-Induced 4 hr. 1131-loss from the thyroid, but prevented the action of TSH when injected 17 hr. before the hormone. The findings suggest that act D a) does not interfere with thyroidal iodide transport and iodine binding, nor with the effect of TSH on the former, b) may block the formation of an antagonist of TSH on the thyroidal iodide pump, and, c) if allowed to act long enough, can prevent the action of TSH whereby it releases iodine from the thyroid.