FUNCTIONAL AND MORPHOLOGICAL-CHANGES OF THE THYROID-GLAND FOLLOWING 5DAYS OF PULSATILE TRH STIMULATION IN MALE-RATS

The aim of the present study was to evaluate in vivo the selective eff ects of a small increase in plasma TSH levels on thyroid function, pro liferation and morphology. Chronically catheterized male Sprague-Dawle y rats were stimulated i.v. over 5 days either with TRH (2 mu g TRH in 100 mu l 0.9% (w/v) NaCl (TRH-P) or the NaCl carrier alone (P), both given as pulses every 2 h. Control groups were cotreated i.v. with 10 mu g thyroxine ((T)4)/100 g body weight per day (TRH-P+T-4) starting 2 days before pulsatile stimulation. TSH plasma levels were approximate ly doubled by TRH-P (P less than or equal to 0.001), T-4 plasma levels significantly increased (P less than or equal to 0.001) but tri-iodot hyronine plasma levels did not change compared with treatment with P. No significant changes between groups were found in thyroid weight and in intrathyroidal iodine content, but the percentage of 5-bromo-2'-de soxyuridine-labelled thyrocytes as a marker of proliferation in TRH-P- treated animals was significantly increased over P or TRH-P+T-4 (P les s than or equal to 0.001). Ultrastructural analysis of the thyroid eva luated by electron microscopy revealed a significant increase in the n umber of lysosomes (P less than or equal to 0.001). The size of the en doplasmic reticulum (ER) in relation to the cytoplasm was significantl y increased when treated with TRH-P compared with P or TRH-P+T-4 (P le ss than or equal to 0.001). Post-embedding immunogold staining reveale d Tg as a major product within ER cisternae. Immunogold labelling was moderate in controls and higher densities of gold particles were obtai ned in TRH-P-treated animals (P less than or equal to 0.001). In concl usion, short-term pulsatile TRH stimulation increasing the plasma leve ls of immunoreactive TSH only twofold is capable of inducing hypertrop hy of the thyrocytes by gross ultrastructural changes which are parall eled by an increase in circulating T-4. These data underscore the domi nant role of TSH on thyroid ultrastructure within the narrow boundarie s of normal physiological regulation.