The effect of elevated doses of thyrotropin on mouse thyroid.

In the course of validating the McKenzie assay it was found that large doses of bovine or rat TSH have a retarding effect on hormonal secretion from the thyroid. TSH in doses less than 10 mU had a maximal effect on thyroidal secretion at about 2-3 h after administration. Doses of TSH in excess of 10 mU caused the peak of secretion to appear at about 9-10 h and caused, as well, a decreased thyroidal iodine release at earlier times. This effect was not due to changes in the pattern of iodocompounds secreted by the thyroid or to a change in the clearance of the blood [125I] thyroxine. An estimate of the integrated secretion with time was linear with log dose up to 100 mU TSH. This pattern of response to TSH is also seen when colloid droplet formation is the parameter studied. cAMP accumulation shows a different pattern of response to TSH. Control levels of cAMP were 1-2 pmoles/mg thyroid. Doses of TSH smaller than 5 mU caused no significant increase in cAMP. With a further increase in TSH up to 200 mU per mouse, cAMP levels increased linearly with the log of TSH and reached 400 pmoles/mg thyroid. Theophylline administered together with large doses of TSH increased the level of the thyroidal cAMP and further decreased the release of iodocompounds at 2 h. These results indicate that there may be an intrathyroidal mechanism which prevents a surge of secretion of thyroid hormones with acute changes in blood TSH levels. The mechanism sensitive to excess TSH is probably associated with steps in thyroidal activation between the accumulation of cAMP and colloid droplet formation.