Abstract
The relationship between the binding of L-triiodothyronine (T3) to nuclear receptors and the induction of growth hormone synthesis was examined in cultured GH1 cells, a rat pituitary cell line. After 24 hr, T3 induced a maximal 4-fold increase in the rate of growth hormone wynthesis; the T3 concentration that induced a half-maximal increase was 0.22 nM. The biologic dose-response curve was shifted to the left of the receptor occupancy curve (Kd = 0.5 nM) by a factor of approximately 2 when receptor binding was examined for 4 hr but showed a significantly closer agreement when examined for the same 24-hr period as the biologic response. This shift in the fractional occupancy curve is not due to further equilibration but occurs as a result of a time- and dose-dependent depletion of the nuclear receptor by T3.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DeGroot L. J., Strausser J. L. Binding of T3 in rat liver nuclei. Endocrinology. 1974 Jul;95(1):74–83. doi: 10.1210/endo-95-1-74. [DOI] [PubMed] [Google Scholar]
- Gavin J. R., 3rd, Roth J., Neville D. M., Jr, de Meyts P., Buell D. N. Insulin-dependent regulation of insulin receptor concentrations: a direct demonstration in cell culture. Proc Natl Acad Sci U S A. 1974 Jan;71(1):84–88. doi: 10.1073/pnas.71.1.84. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Koerner D., Schwartz H. L., Surks M. I., Oppenheimer J. H. Binding of selected iodothyronine analogues to receptor sites of isolated rat hepatic nuclei. High correlation between structural requirements for nuclear binding and biological activity. J Biol Chem. 1975 Aug 25;250(16):6417–6423. [PubMed] [Google Scholar]
- Lesniak M. A., Roth J., Gorden P., Gavin J. R., 3rd Human growth hormone radioreceptor assay using cultured human lymphocytes. Nat New Biol. 1973 Jan 3;241(105):20–22. doi: 10.1038/newbio241020a0. [DOI] [PubMed] [Google Scholar]
- Lesniak M. A., Roth J. Regulation of receptor concentration by homologous hormone. Effect of human growth hormone on its receptor in IM-9 lymphocytes. J Biol Chem. 1976 Jun 25;251(12):3720–3729. [PubMed] [Google Scholar]
- Mickey J., Tate R., Lefkowitz R. J. Subsensitivity of adenylate cyclase and decreased beta-adrenergic receptor binding after chronic exposure to (minus)-isoproterenol in vitro. J Biol Chem. 1975 Jul 25;250(14):5727–5729. [PubMed] [Google Scholar]
- Oppenheimer J. H., Schwartz H. L., Koerner D., Surks M. I. Limited binding capacity sites for L-triiodothyronine in rat liver nuclei. Nuclear-cytoplasmic interrelation, binding constants, and cross-reactivity with L-thyroxine. J Clin Invest. 1974 Mar;53(3):768–777. doi: 10.1172/JCI107615. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oppenheimer J. H., Schwartz H. L., Surks M. I. Nuclear binding capacity appears to limit the hepatic response to L-triiodothyronine (T3). Endocr Res Commun. 1975;2(4-5):309–325. doi: 10.1080/07435807509089004. [DOI] [PubMed] [Google Scholar]
- Samuels H. H., Shapiro L. E. Thyroid hormone stimulates de novo growth hormone synthesis in cultured GH1 cells: evidence for the accumulation of a rate limiting RNA species in the induction process. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3369–3373. doi: 10.1073/pnas.73.10.3369. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Samuels H. H., Tsai J. S., Casanova J., Stanley F. Thyroid hormone action: in vitro characterization of solubilized nuclear receptors from rat liver and cultured GH1 cells. J Clin Invest. 1974 Oct;54(4):853–865. doi: 10.1172/JCI107825. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Samuels H. H., Tsai J. S. Thyroid hormone action in cell culture: domonstration of nuclear receptors in intact cells and isolated nuclei. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3488–3492. doi: 10.1073/pnas.70.12.3488. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Samuels H. H., Tsai J. S. Thyroid hormone action. Demonstration of similar receptors in isolated nuclei of rat liver and cultured GH1 cells. J Clin Invest. 1974 Feb;53(2):656–659. doi: 10.1172/JCI107601. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spindler B. J., MacLeod K. M., Ring J., Baxter J. D. Thyroid hormone receptors. Binding characteristics and lack of hormonal dependency for nuclear localization. J Biol Chem. 1975 Jun 10;250(11):4113–4119. [PubMed] [Google Scholar]
- Tsai J. S., Samuels H. H. Thyroid hormone action: stimulation of growth hormone and inhibition of prolactin secretion in cultured GH1 cells. Biochem Biophys Res Commun. 1974 Jul 10;59(1):420–428. doi: 10.1016/s0006-291x(74)80223-8. [DOI] [PubMed] [Google Scholar]
