Insulin and insulin-like growth factor-I inhibit thyrotropin-increased iodide transport in serum-depleted FRTL-5 rat thyroid cells: modulation of adenosine 3',5'-monophosphate signal action.
Insulin enhances the ability of TSH to induce iodide uptake in FRTL-5 rat thyroid cells maintained in 5% serum; however, in cells maintained in 0.2% serum, insulin inhibits the ability of TSH to induce iodide uptake. Since the inhibitory action of insulin is duplicated by 100-fold lower concentrations of insulin-like growth factor-I (IGF-I), inhibition appears to be mediated by the IGF-I receptor. Insulin and IGF-I inhibit the action of a cAMP analog to induce iodide uptake in a manner identical to TSH, but do not inhibit basal or TSH-increased cAMP levels; inhibition, thus, results from regulation of cAMP signal action rather than cAMP signal generation. Inhibition is associated with a more than 2-fold decrease in the maximum velocity of iodide influx, a less than 15% change in the rate of iodide efflux, and no change in the Km for iodide influx, i.e. inhibition effectively results from a decrease in the number of iodide porters. The inhibitory action of insulin/IGF-I is not additive with hydrocortisone, which, under the same conditions, also inhibits TSH- or cAMP-induced iodide porter activity. Actinomycin-D, given 24 h after TSH, superinduces TSH-induced iodide porter activity and abolishes the inhibition by insulin, IGF-I, and/or hydrocortisone; a similar paradoxical effect of actinomycin-D under these conditions has been explained by its ability to inhibit the action of a cAMP-induced factor that increases mRNA degradation. The inhibitory actions of insulin, IGF-I, and hydrocortisone on cAMP-induced iodide porter activity contrast with their simultaneous and synergistic stimulation of the transcriptional action of cAMP on DNA and thyroglobulin synthesis under these conditions.
Saji
M
M
Section on Cell Regulation, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Kohn
L D
LD
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001790:Blood Physiological Phenomena; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology*; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007454:Iodides / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology*
D007328:Insulin; D007454:Iodides; D007334:Insulin-Like Growth Factor I; D013972:Thyrotropin; D000242:Cyclic AMP