Effects of Long Term Thyroxine Treatment on Thyrotropin-Induced Exocytosis and Endocytosis in the Rat Thyroid*

Rats were treated with daily doses of T4 (20 μg, sc) for 2, 7, 14, and 21 days in order to suppress secretion of TSH and thereby decrease thyroid protein synthesis. Twenty minutes before perfusion fixation of the thyroids, the animals were given either TSH (0.5 IU, iv) or saline. The number of endocytotic structures (pseudopods and colloid droplets) were counted in the light microscope. The membrane surface areas of exocytotic vesicles, apical plasma membrane, and endocytotic structures were estimated by electron microscopic stereology. Light microscopy showed that the number of endocytotic structures induced by TSH decreased with increasing time of T4 treatment. Electron microscopy showed that in all non-TSHtreated groups the follicle cells contained exocytotic vesicles but their number and size and, hence, their membrane surface area decreased progressively during T4 treatment. Administration of TSH induced exocytosis, resulting in a reduction of the surface area of the exocytotic vesicles; in relative terms, this reduction was similar in all groups and exceeded 85%. TSH also induced endocytosis in all groups, but the membrane surface area of the endocytotic structures decreased with increasing time of T4 treatment. The sum of the surface areas of the endocytotic structures and the remaining exocytotic vesicles in the TSHtreated groups was almost identical to the surface area of the exocytotic vesicles in the corresponding non-TSH-injected groups. In view of our previous finding that exocytosis results in addition of exocytotic vesicle membrane to the apical plasma membrane, the present observations suggest that the size of the pool of exocytotic vesicles in the follicle cells determines the size of the endocytotic response to a large dose of TSH.