The Anatomy of Secretion in the Follicular Cell of the Thyroid Gland

This study is the third in a series devoted to analyzing secretory phenomena in the thyroid follicular cell. The first and second dealt, respectively, with the fine structure of the cell under normal conditions and after acute stimulation with T S H (1, 2). In this study, we report biochemical data on the effect of acute stimulation with T S H on protein synthesis in the thyroid gland and correlate these data with the results of the earlier morphological studies. Chronically elevated or depressed circulating levels of T S H affect the amount of thyroglobulin, the secretory product of follicular cells, stored in the gland as follicular colloid: elevated levels lead to its depletion, whereas depressed levels lead to its accumulation. These changes may be interpreted to indicate that the turnover of thyroglobulin is regulated by means of TSH. Although there is little reason to question this interpretation, the effects of T S H on individual steps in the turnover cycle, i.e., the secretion, storage, and resorption of thyroglobulin, have not been thoroughly analyzed. In the past, the effect of T S H on thyroglobulin secretion has been evaluated on the basis of morphological data. The appearance of numerous large colloid droplets in the apical cytoplasm of follicular cells minutes after the thyroid is stimulated with T S H was interpreted, until recently, to denote accelerated synthesis of thyroglobulin. However, on the basis of evidence from radioautographic and histochemical studies (3-5), the droplets are now considered to contain thyroglobulin phagocytized by follicular cells from the follicular lumen, as the initial step in its breakdown. Under these circumstances, the numbers of intraepithelial colloid droplets should no longer be considered indicators of increased protein synthetic activity in follicular cells. Several aspects of protein synthesis in the thyroid gland have been examined with biochemical techniques. Debons and Pitman (6) observed that incubation with T S H resulted in increased uptake of amino acid by bovine and canine thyroid slices, but Raghupathy et al. (7) did not confirm this finding in similar experiments with ovine thyroid slices. Raghupathy et el. (8) observed that thyroid slices from guinea pigs pretreated with T S H showed increased incorporation of amino acid into protein. The increase was first detected 10 to 15 hr after t reatment with the hormone began. In a preliminary account of a similar study, Schneider and Goldberg (26) report increased incorporation of amino acid by thyroid slices from hypophysectomized rats pretreated with TSH. However, in their study the response to stimulation was more rapid, reaching a peak 8 hr following a single injection of TSH. Exposure of ovine thyroid slices to T S H in vitro does not stimulate incorporation of amino acid into protein (7).