Iodothyronine release from the perfused canine thyroid following cessation of stimulation: rapid decline of triiodothyronines in comparison with thyroxine

The kinetics of thyroid secretion after termination of stimulation by 100 muU/ml bovine thyroid stimulating hormone (TSH) or 5 mM cyclic AMP (cAMP) were studied using perfused canine thyroid lobes. All experiments were performed as paired comparisons, one thyroid lobe acting as a control continuing to receive infusion of the stimulator. 2.5 h after termination of TSH infusion, the secretion of thyroxine (T(4)), 3,5,3'-triiodothyronine (T(3)), and 3,3',5'-triiodothyronine (rT(3)) was not significantly different from that of the control lobes. After cessation of cAMP infusion, the secretion of T(4) continued unaffected for approximately 40 min. Then a gradual decline in T(4) release occurred. The secretion of T(3) and rT(3) decreased somewhat earlier leading to a transient phase with increases in the T(4):T(3) and T(4):rT(3) ratios in the thyroid effluent. The persistently high secretion of iodothyronines despite cessation of TSH infusion is most likely the result of a continued stimulation by receptor-bound TSH. Because the clearance of intracellular cAMP is rapid and the concentration of cAMP used for stimulation in these experiments only exceeded the concentration necessary for eliciting a secretory response modestly, it is reasonable to assume that stimulation of colloid droplet formation stopped shortly after termination of cAMP infusion. The bulk of iodothyronines secreted thereafter thus originated from continued hydrolysis of thyroglobulin engulfed by the follicular cells during the preceding cAMP infusion. The pattern of an earlier decline in secretion of T(3) and rT(3) than of T(4) from this intracellular pool of thyroglobulin points to a more rapid liberation of triiodothyronines than of thyroxine from thyroglobulin during intracellular hydrolysis.