Requirement of insulin growth factor I plus hydrocortisone for the regeneration of thyrotropin (TSH)-dependent mechanism of I-efflux and Ca2+ mobilization in FRTL-5 cells during TSH depletion.

FRTL-5 rat thyroid cells grown in culture medium supplemented with serum and 6H (TSH, insulin, hydrocortisone, transferrin, glycylhistidyllysine, and somatostatin) showed a significant increase in TSH-dependent cAMP accumulation and I- efflux after prolonged incubation (5 to 10 days) of the cells in culture medium containing 5H (6H - TSH) or serum. The induction of the cAMP response was at least partly reproduced when both serum and 5H were omitted from the medium. However the I- efflux response was completely abolished under such conditions and regenerated when serum or 5H was present. The serum or 5H effect on I- efflux response was mimicked by 2H (insulin + hydrocortisone). Insulin was replaced by 1/1000 less insulin-like growth factor-I than insulin. TSH-dependent Ca2+ mobilization of the cells was similarly affected by the presence of serum or 2H. However, the I- efflux and Ca2+ responses to an agonist other than TSH (extracellular ATP) were not substantially influenced by serum and/or 2H as well as TSH in the medium. The results indicate that serum or insulin-like growth factor-I plus hydrocortisone are required rather specifically for the regeneration of the TSH-receptor mechanism coupled with I- efflux and/or Ca2+ mobilization mechanism.