Regulation of thyroid hormone synthesis in cultured ovine thyroid follicles.

Primary cultures of sheep thyroid follicles were used to study the regulatory control mechanisms of thyroid hormone production. When maintained under serum-free conditions in vitro these follicles exhibit hormone-dependent iodide transport, iodine organification, and physiological de novo thyroid hormone formation. In previous studies we have also shown that thyroid follicles condition their culture media with insulin-like growth factors (IGFs) and IGF-binding proteins which are of potential autocrine or paracrine significance in thyroid hormonogenesis. TSH (100 microU/ml) alone modestly stimulated iodine uptake and organification, which was further potentiated by pharmacological or physiological concentrations of insulin and by physiological concentrations of IGF-I or IGF-II. A combination of TSH and cortisol (10 nM) optimally stimulated iodine uptake and organification without additive or synergistic effects among combinations of cortisol with insulin or IGFs. Insulin, IGF-I, IGF-II, or cortisol alone were without effect on iodine uptake and organification. The effect of TSH was mimicked by forskolin or (Bu)2cAMP, and the synergistic effect of cortisol with TSH was duplicated in incubations of dexamethasone with TSH. In long term studies of the same experimental conditions, with 10(-6) M NaI added to the culture medium, an increase in radioimmunoassayable T4 and T3 in conditioned cell culture media and cell layer extracts was confirmed for all conditions, with the exception of physiological concentrations of insulin. IGF-I and IGF-II were equipotent in their stimulation of thyroid hormonogenesis in the presence of TSH. The effect of high concentrations of insulin may be explained by a combined action through insulin and type I IGF receptors. We have previously reported that the stimulation of iodine uptake and organification (de novo thyroid hormone formation here) by TSH and cortisol is inversely correlated with their inhibition of IGF-binding proteins released by the cells while IGF release is unchanged. Overall, these data suggest that the regulation of thyroid hormonogenesis involves the endocrine hormones TSH and cortisol, acting in synergy with locally produced IGFs.