Effects of Thyrotropin on Thyroglobulin Exocytosis and Iodination in the Rat Thyroid Gland*

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Abstract
Rats, pretreated with thyroxine for 2 days, were given 1 or 2 i.v. injections of 500 mU [units] of TSH [thyroid stimulating hormone]; in some groups the 2nd TSH dose was replaced by 0.75 .mu.mol isoproterenol. The effects of the thyroid stimulators on the following parameters were studied: the number of exocytotic vesicles in the follicle cells; the incorporation of 125I into thyroid proteins, measured over periods of 5 min; and the thyroidal c[cyclic]AMP contents. At 2 h after TSH administration, a 2nd dose of TSH failed to stimulate iodination while at 8 h the iodination response was normal. Two hours after TSH the follicle cells contained practically no exocytotic vesicles but at 8 h they had a full supply of vesicles, and this was emptied by the 2nd TSH injection. The cAMP content was less increased by the 2nd TSH injection than by the first one, but the stimulatory effect of the 2nd TSH dose on cAMP was the same at 2 h and at 8 h; the lack of iodination response at 2 h was apparently not simply due to blocking of TSH receptors. Isoproterenol, which acts on other receptors than does TSH, caused a similar cAMP increase in controls and at 2 h and 8 h after TSH, but stimulated iodination only in controls and at 8 h after TSH; this supported the conclusion that the lack of iodination response to a 2nd TSH dose at 2 h was not due to impairment of the adenylate cyclase-cAMP system. A rapid iodination response to TSH depends on stimulated exocytosis which, in turn, requires a pool of exocytotic vesicles in the follicle cells. Such a coupling between exocytosis and iodination seems appropriate since by exocytosis uniodinated thyroglobulin and membrane, showing peroxidase activity histochemically, are delivered to the site of iodination, the apical cell surface.