Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1985 Aug;76(2):890–893. doi: 10.1172/JCI112049

Metabolic effect of 3,3',5'-triiodothyronine in cultured growth hormone-producing rat pituitary tumor cells. Evidence for a unique mechanism of thyroid hormone action.

D L St Germain
PMCID: PMC423928  PMID: 4031075

Abstract

Physiologic levels of 3,3',5'-triiodothyronine (rT3) are generally believed to have minimal metabolic effects in the pituitary gland and other tissues. In the present studies, the regulatory role of rT3 and other thyroid hormones on iodothyronine 5'-deiodinase (I5'D) activity was studied in a growth hormone-producing rat pituitary tumor cell line (GH3 cells). I5'D activity was thiol-dependent and displayed nonlinear reaction kinetics suggesting the presence of two enzymatic processes, one having a low Michaelis constant (Km for thyroxine [T4] of 2 nM) and a second with a high Km value (0.9 microM). Growth of cells in hormone-depleted medium resulted in a two- to 3.5-fold increase in low Km I5'D activity (P less than 0.001). The addition of thyroid hormones to the culture medium resulted in a rapid, dose-dependent inhibition of low Km I5'D activity with the following order of analogue potency: rT3 greater than or equal to T4 greater than 3,5,3'-triiodothyronine (T3). Using serum-free culture conditions, rT3 was approximately 50 times more active than T3. These inhibitory effects were noted within 15 min of hormone addition and could not be attributed to substrate competition with T4. These findings suggest that the control of T4 to T3 conversion by thyroid hormones in the anterior pituitary gland is mediated by a unique cellular mechanism that is independent of the nuclear T3 receptor; and under some circumstances, rT3 may play a regulatory role in controlling this enzymatic process.

Full text

PDF
890

Images in this article

891Image
on p.891

Selected References

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

  1. Chopra I. J. A study of extrathyroidal conversion of thyroxine (T4) to 3,3',5-triiodothyronine (T3) in vitro. Endocrinology. 1977 Aug;101(2):453–463. doi: 10.1210/endo-101-2-453. [DOI] [PubMed] [Google Scholar]
  2. Galton V. A. Binding of thyroid hormones in serum and liver cytosol of Rana catesbeiana tadpoles. Endocrinology. 1980 Jul;107(1):61–69. doi: 10.1210/endo-107-1-61. [DOI] [PubMed] [Google Scholar]
  3. Hinkle P. M., Perrone M. H., Greer T. L. Thyroid hormone action in pituitary cells. Differences in the regulation of thyrotropin-releasing hormone receptors and growth hormone synthesis. J Biol Chem. 1979 May 25;254(10):3907–3911. [PubMed] [Google Scholar]
  4. Kaptein E. M., Robinson W. J., Grieb D. A., Nicoloff J. T. Peripheral serum thyroxine, triiodothyronine and reverse triiodothyronine kinetics in the low thyroxine state of acute nonthyroidal illnesses. A noncompartmental analysis. J Clin Invest. 1982 Mar;69(3):526–535. doi: 10.1172/JCI110478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  6. 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]
  7. Larsen P. R., Silva J. E., Kaplan M. M. Relationships between circulating and intracellular thyroid hormones: physiological and clinical implications. Endocr Rev. 1981 Winter;2(1):87–102. doi: 10.1210/edrv-2-1-87. [DOI] [PubMed] [Google Scholar]
  8. Leonard J. L., Silva J. E., Kaplan M. M., Mellen S. A., Visser T. J., Larsen P. R. Acute posttranscriptional regulation of cerebrocortical and pituitary iodothyronine 5'-deiodinases by thyroid hormone. Endocrinology. 1984 Mar;114(3):998–1004. doi: 10.1210/endo-114-3-998. [DOI] [PubMed] [Google Scholar]
  9. Melmed S., Nelson M., Kaplowitz N., Yamada T., Hershman J. M. Glutathione-dependent thyroxine 5'-monodeiodination modulates growth hormone production by cultured nonthyrotropic rat pituitary cells. Endocrinology. 1981 Mar;108(3):970–976. doi: 10.1210/endo-108-3-970. [DOI] [PubMed] [Google Scholar]
  10. Nicod P., Burger A., Strauch G., Vagenakis A. G., Braverman L. E. The failure of physiologic doses of reverse T3 to effect thyroid-pituitary function in man. J Clin Endocrinol Metab. 1976 Aug;43(2):478–481. doi: 10.1210/jcem-43-2-478. [DOI] [PubMed] [Google Scholar]
  11. Oppenheimer J. H. Thyroid hormone action at the cellular level. Science. 1979 Mar 9;203(4384):971–979. doi: 10.1126/science.218285. [DOI] [PubMed] [Google Scholar]
  12. Papavasiliou S. S., Martial J. A., Latham K. R., Baxter J. D. Thyroid hormonelike actions of 3,3',5'-L-triiodothyronine nad 3,3'-diiodothyronine. J Clin Invest. 1977 Dec;60(6):1230–1239. doi: 10.1172/JCI108882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Samuels H. H., Stanley F., Casanova J. Depletion of L-3,5,3'-triiodothyronine and L-thyroxine in euthyroid calf serum for use in cell culture studies of the action of thyroid hormone. Endocrinology. 1979 Jul;105(1):80–85. doi: 10.1210/endo-105-1-80. [DOI] [PubMed] [Google Scholar]
  14. Samuels H. H., Stanley F., Casanova J. Relationship of receptor affinity to the modulation of thyroid hormone nuclear receptor levels and growth hormone synthesis by L-triiodothyronine and iodothyronine analogues in cultured GH1 cells. J Clin Invest. 1979 Jun;63(6):1229–1240. doi: 10.1172/JCI109418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Samuels H. H., Tsai J. S., Cintron R. Thyroid hormone action: a cell-culture system responsive to physiological concentrations of thyroid hormones. Science. 1973 Sep 28;181(4106):1253–1256. doi: 10.1126/science.181.4106.1253. [DOI] [PubMed] [Google Scholar]
  16. Shulkin B. L., Utiger R. D. Reverse triiodothyronine does not alter pituitary-thyroid function in normal subjects. J Clin Endocrinol Metab. 1984 Jun;58(6):1184–1187. doi: 10.1210/jcem-58-6-1184. [DOI] [PubMed] [Google Scholar]
  17. Silva J. E., Leonard J. L. Regulation of rat cerebrocortical and adenohypophyseal type II 5'-deiodinase by thyroxine, triiodothyronine, and reverse triiodothyronine. Endocrinology. 1985 Apr;116(4):1627–1635. doi: 10.1210/endo-116-4-1627. [DOI] [PubMed] [Google Scholar]
  18. St Germain D. L., Adler R. A., Galton V. A. Thyroxine 5'-deiodinase activity in anterior pituitary glands transplanted under the renal capsule in the rat. Endocrinology. 1985 Jul;117(1):55–63. doi: 10.1210/endo-117-1-55. [DOI] [PubMed] [Google Scholar]
  19. St Germain D. L., Galton V. A. Comparative study of pituitary-thyroid hormone economy in fasting and hypothyroid rats. J Clin Invest. 1985 Feb;75(2):679–688. doi: 10.1172/JCI111747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Surks M. I., Fels E. C., DeFesi C. R. Induction of amino acid transport by L-triiodothyronine in cultured growth hormone-producing rat pituitary tumor cells (GC cells). J Biol Chem. 1984 May 10;259(9):5726–5733. [PubMed] [Google Scholar]
  21. Tashjian A. H., Jr Clonal strains of hormone-producing pituitary cells. Methods Enzymol. 1979;58:527–535. doi: 10.1016/s0076-6879(79)58167-1. [DOI] [PubMed] [Google Scholar]
  22. Visser T. J., Kaplan M. M., Leonard J. L., Larsen P. R. Evidence for two pathways of iodothyronine 5'-deiodination in rat pituitary that differ in kinetics, propylthiouracil sensitivity, and response to hypothyroidism. J Clin Invest. 1983 Apr;71(4):992–1002. doi: 10.1172/JCI110854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Visser T. J., Leonard J. L., Kaplan M. M., Larsen P. R. Kinetic evidence suggesting two mechanisms for iodothyronine 5'-deiodination in rat cerebral cortex. Proc Natl Acad Sci U S A. 1982 Aug;79(16):5080–5084. doi: 10.1073/pnas.79.16.5080. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES