Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1979 Jul;64(1):265–271. doi: 10.1172/JCI109447

In Vitro and In Vivo Refractoriness to Thyrotropin Stimulation of Iodine Organification and Thyroid Hormone Secretion

James B Field 1,2, Andrew Dekker 1,2, Gail Titus 1,2, Mary Eleanor Kerins 1,2, William Worden 1,2, Rosalyn Frumess 1,2
PMCID: PMC372113  PMID: 221545

Abstract

Earlier studies indicated that initial exposure of thyroid slices to thyrotropin diminished responsiveness of the adenylate cyclase-cyclic AMP system, glucose oxidation, and 32Pi incorporation into phospholipids upon readdition of the hormone. The present studies demonstrate that slices from dog, beef, and human thyroid glands initially incubated with thyrotropin (TSH) were less responsive to subsequent addition of the hormone when organification of iodide was examined. Increasing the amount of TSH did not overcome the refractoriness induced by the initial exposure to the hormone. Furthermore, the stimulatory effects of dibutyryl cyclic AMP and prostagladin E1 were abolished in slices previously incubated with TSH. Development of such refractoriness did not depend upon new protein synthesis and was not abolished by 1 mM prophylthiouracil in the first incubation. Addition of 0.1 μM thyroxine or triiodothyronine or 1.5 μM iodide during all three incubations did not modify the response to TSH, added for the first time in the third incubation. However, 1 mM iodide in the buffer during all three incubations inhibited the response to TSH during the third incubation. During the refractory period, effects of TSH on colloid droplet formation were also diminished. The in vivo effect of TSH on serum l- triiodothyronine in rats was significantly reduced when the rats had been injected with TSH 8 h earlier. These studies demonstrate that TSH-induced refractoriness also includes effects on organification of iodine and secretion of thyroid hormone. The results cannot be adequately explained by unresponsiveness of adenylate cyclase because effects of dibutyryl cyclic AMP and prostagladin E1 were also inhibited by prior exposure to TSH.

Full text

PDF
265

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahn C. S., Rosenberg I. N. Iodine metabolism in thyroid slices: effects of TSH, dibutyryl cyclic 3',5'-AMP, NaF and prostaglandin E-1. Endocrinology. 1970 Feb;86(2):396–405. doi: 10.1210/endo-86-2-396. [DOI] [PubMed] [Google Scholar]
  2. Björkman U., Ekholm R., Ericson L. E. Effects of thyrotropin on thyroglobulin exocytosis and iodination in the rat thyroid gland. Endocrinology. 1978 Feb;102(2):460–470. doi: 10.1210/endo-102-2-460. [DOI] [PubMed] [Google Scholar]
  3. Burke G. Effects of iodide on thyroid stimulation. J Clin Endocrinol Metab. 1970 Jan;30(1):76–84. doi: 10.1210/jcem-30-1-76. [DOI] [PubMed] [Google Scholar]
  4. Croxson M. S., Hall T. D., Nicoloff J. T. Failure of triiodothyronine to inhibit TSH-mediated thyroid hormone release in man. J Clin Endocrinol Metab. 1977 Sep;45(3):593–596. doi: 10.1210/jcem-45-3-593. [DOI] [PubMed] [Google Scholar]
  5. Dekker A., Field J. B. Correlation of effects of thyrotropin, prostaglandins and ions on glucose oxidation, cyclic-AMP, and colloid droplet formation in dog thyroid slices. Metabolism. 1970 Jun;19(6):453–464. doi: 10.1016/0026-0495(70)90097-1. [DOI] [PubMed] [Google Scholar]
  6. Field J. B., Bloom G., Chou C., Kerins M. E. Inhibition of thyroid-stimulating hormone stimulation of protein kinase, glucose oxidation, and phospholipid synthesis in thyroid slices previously exposed to the hormone. J Clin Invest. 1977 Apr;59(4):659–665. doi: 10.1172/JCI108684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Field J. B., Bloom G., Kerins M. E., Chayoth R., Zor U. Activation of protein kinase in thyroid slices by thyroid-stimulating hormone. J Biol Chem. 1975 Jul 10;250(13):4903–4910. [PubMed] [Google Scholar]
  8. Friedman Y., Lang M., Burke G. Inhibition of thyroid adenylate cyclase by thyroid hormone: a possible locus for the "short-loop" negative feedback phenomenon. Endocrinology. 1977 Sep;101(3):858–868. doi: 10.1210/endo-101-3-858. [DOI] [PubMed] [Google Scholar]
  9. Gafni M., Sirkis N., Gross J. Inhibition of the response of mouse thyroid to tryrotropin induced by chronic triiodothyronine treatment. Endocrinology. 1975 Nov;97(5):1256–1262. doi: 10.1210/endo-97-5-1256. [DOI] [PubMed] [Google Scholar]
  10. Kaneko T., Zor U., Field J. B. Thyroid-stimulating hormone and prostaglandin E1 stimulation of cyclic 3',5'-adenosine monophosphate in thyroid slices. Science. 1969 Mar 7;163(3871):1062–1063. doi: 10.1126/science.163.3871.1062. [DOI] [PubMed] [Google Scholar]
  11. Kaneko Y. Cyclic AMP level of human thyroid cells in monolayer culture. TSH induced refractoriness to TSH action. Horm Metab Res. 1976 May;8(3):202–206. doi: 10.1055/s-0028-1093660. [DOI] [PubMed] [Google Scholar]
  12. Larsen P. R. Direct immunoassay of triiodothyronine in human serum. J Clin Invest. 1972 Aug;51(8):1939–1949. doi: 10.1172/JCI107000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Rapoport B., Adams R. J. Induction of refractoriness to thyrotropin stimulation in cultured thyroid cells. Dependence on new protein synthesis. J Biol Chem. 1976 Nov 10;251(21):6653–6661. [PubMed] [Google Scholar]
  14. Riesco G., Taurog A., Larsen R., Krulich L. Acute and chronic responses to iodine deficiency in rats. Endocrinology. 1977 Feb;100(2):303–313. doi: 10.1210/endo-100-2-303. [DOI] [PubMed] [Google Scholar]
  15. Sherwin J. R., Tong W. Thyroidal autoregulation. Iodide-induced suppression of thyrotropin-stimulated cyclic AMP production and iodinating activity in thyroid cells. Biochim Biophys Acta. 1975 Sep 8;404(1):30–39. [PubMed] [Google Scholar]
  16. Shuman S. J., Zor U., Chayoth R., Field J. B. Exposure of thyroid slices to thyroid-stimulating hormone induces refractoriness of the cyclic AMP system to subsequent hormone stimulation. J Clin Invest. 1976 May;57(5):1132–1141. doi: 10.1172/JCI108380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Van Sande J., Dumont J. E. Effects of thyrotropin, prostaglandin E1 and iodide on cyclic 3',5'-AMP concentration in dog thyroid slices. Biochim Biophys Acta. 1973 Jul 28;313(2):320–328. doi: 10.1016/0304-4165(73)90031-7. [DOI] [PubMed] [Google Scholar]
  18. Verrier B., Cailla H. L. Endogenous cyclic AMP in thyroid cell culture. Effect of thyroid-stimulating hormone and dibutyryl cyclic AMP. Biochim Biophys Acta. 1976 Mar 25;428(1):233–239. doi: 10.1016/0304-4165(76)90124-0. [DOI] [PubMed] [Google Scholar]
  19. Yu S., Friedman Y., Richman R., Burke G. Altered thyroidal responsivity to thyrotropin induced by circulating thyroid hormones. A "short-loop" regulatory mechanism? J Clin Invest. 1976 Mar;57(3):745–755. doi: 10.1172/JCI108333. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES