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. 1995 Jul 15;309(Pt 2):667–675. doi: 10.1042/bj3090667

Regulation of myo-inositol transport during the growth and differentiation of thyrocytes: a link with thyroid-stimulating hormone-induced phospholipase A2 activity.

G Grafton 1, M A Baxter 1, M C Sheppard 1, M C Eggo 1
PMCID: PMC1135782  PMID: 7626034

Abstract

The Vmax of myo-inositol transport increased 3-fold during epidermal growth factor (EGF)-induced growth and thyroid-stimulating hormone. (TSH)-induced differentiation in primary cultures of sheep and human thyrocytes. The Km remained unaltered. This up-regulation required the presence of insulin. The TSH-induced rise in myo-inositol transport commenced 8 to 16 h after the initial stimulus and achieved a plateau at 24 h. In human thyrocytes the change in Vmax was accompanied by an increase in the steady-state levels of mRNA for the myo-inositol transporter following treatment with either ligand. Examination of the metabolites of myo-inositol showed few significant changes after treatment of sheep thyrocytes with EGF for 24 h. This is consistent with maintenance of the intracellular concentration of myo-inositol as the cells enlarge in preparation for cell division. In TSH-treated cells, however, up-regulation of myo-inositol transport was linked with increased myo-inositol cycling across the cell membrane, increased phospholipase A2-mediated turnover of phosphatidylinositol and a concomitant increase in arachidonic acid turnover. Increased levels of myo-inositol phosphates were also noted 24 h after TSH treatment. These results indicate the initiation of secondary signalling events many hours after the primary stimulus.

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Selected References

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

  1. Alonso T., Santos E. Increased intracellular glycerophosphoinositol is a biochemical marker for transformation by membrane-associated and cytoplasmic oncogenes. Biochem Biophys Res Commun. 1990 Aug 31;171(1):14–19. doi: 10.1016/0006-291x(90)91349-w. [DOI] [PubMed] [Google Scholar]
  2. Bachrach L. K., Eggo M. C., Mak W. W., Burrow G. N. Phorbol esters stimulate growth and inhibit differentiation in cultured thyroid cells. Endocrinology. 1985 Apr;116(4):1603–1609. doi: 10.1210/endo-116-4-1603. [DOI] [PubMed] [Google Scholar]
  3. Baxter M. A., Bunce C. M., Lord J. M., French P. J., Michell R. H., Brown G. Changes in inositol transport during DMSO-induced differentiation of HL60 cells towards neutrophils. Biochim Biophys Acta. 1991 Jan 31;1091(2):158–164. doi: 10.1016/0167-4889(91)90056-4. [DOI] [PubMed] [Google Scholar]
  4. Benjamins J. A., Agranoff B. W. Distribution and properties of CDP-diglyceride:inositol transferase from brain. J Neurochem. 1969 Apr;16(4):513–527. doi: 10.1111/j.1471-4159.1969.tb06850.x. [DOI] [PubMed] [Google Scholar]
  5. Berridge M. J. Inositol trisphosphate and calcium signalling. Nature. 1993 Jan 28;361(6410):315–325. doi: 10.1038/361315a0. [DOI] [PubMed] [Google Scholar]
  6. Biden T. J., Wollheim C. B. Active transport of myo-inositol in rat pancreatic islets. Biochem J. 1986 Jun 15;236(3):889–893. doi: 10.1042/bj2360889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bunce C. M., French P. J., Allen P., Mountford J. C., Moor B., Greaves M. F., Michell R. H., Brown G. Comparison of the levels of inositol metabolites in transformed haemopoietic cells and their normal counterparts. Biochem J. 1993 Feb 1;289(Pt 3):667–673. doi: 10.1042/bj2890667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  9. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Clarke N. G., Dawson R. M. Alkaline O leads to N-transacylation. A new method for the quantitative deacylation of phospholipids. Biochem J. 1981 Apr 1;195(1):301–306. doi: 10.1042/bj1950301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Darnell J. C., Osterman D. G., Saltiel A. R. Fatty acid remodelling of phosphatidylinositol under conditions of de novo synthesis in rat liver microsomes. Biochim Biophys Acta. 1991 Jul 30;1084(3):279–291. doi: 10.1016/0005-2760(91)90070-x. [DOI] [PubMed] [Google Scholar]
  12. Eggo M. C., Bachrach L. K., Burrow G. N. Interaction of TSH, insulin and insulin-like growth factors in regulating thyroid growth and function. Growth Factors. 1990;2(2-3):99–109. doi: 10.3109/08977199009071497. [DOI] [PubMed] [Google Scholar]
  13. Eggo M. C., Bachrach L. K., Fayet G., Errick J., Kudlow J. E., Cohen M. F., Burrow G. N. The effects of growth factors and serum on DNA synthesis and differentiation in thyroid cells in culture. Mol Cell Endocrinol. 1984 Dec;38(2-3):141–150. doi: 10.1016/0303-7207(84)90112-6. [DOI] [PubMed] [Google Scholar]
  14. Eggo M. C., Burrow G. N. Integrated regulation of growth and of function. Adv Exp Med Biol. 1989;261:327–339. doi: 10.1007/978-1-4757-2058-7_13. [DOI] [PubMed] [Google Scholar]
  15. Errick J. E., Eggo M. C., Burrow G. N. Epidermal growth factor inhibits thyrotropin-mediated synthesis of tissue-specific proteins in cultured ovine thyroid cells. Mol Cell Endocrinol. 1985 Nov;43(1):51–59. doi: 10.1016/0303-7207(85)90041-3. [DOI] [PubMed] [Google Scholar]
  16. Ferguson M. A., Williams A. F. Cell-surface anchoring of proteins via glycosyl-phosphatidylinositol structures. Annu Rev Biochem. 1988;57:285–320. doi: 10.1146/annurev.bi.57.070188.001441. [DOI] [PubMed] [Google Scholar]
  17. French P. J., Bunce C. M., Stephens L. R., Lord J. M., McConnell F. M., Brown G., Creba J. A., Michell R. H. Changes in the levels of inositol lipids and phosphates during the differentiation of HL60 promyelocytic cells towards neutrophils or monocytes. Proc Biol Sci. 1991 Sep 23;245(1314):193–201. doi: 10.1098/rspb.1991.0109. [DOI] [PubMed] [Google Scholar]
  18. Fujimoto J., Brenner-Gati L. Protein kinase-C activation during thyrotropin-stimulated proliferation of rat FRTL-5 thyroid cells. Endocrinology. 1992 Mar;130(3):1587–1592. doi: 10.1210/endo.130.3.1537308. [DOI] [PubMed] [Google Scholar]
  19. Gallo A., Benusiglio E., Bonapace I. M., Feliciello A., Cassano S., Garbi C., Musti A. M., Gottesman M. E., Avvedimento E. V. v-ras and protein kinase C dedifferentiate thyroid cells by down-regulating nuclear cAMP-dependent protein kinase A. Genes Dev. 1992 Sep;6(9):1621–1630. doi: 10.1101/gad.6.9.1621. [DOI] [PubMed] [Google Scholar]
  20. Grafton G., Bunce C. M., Sheppard M. C., Brown G., Baxter M. A. Changes in the kinetics of inositol transport during TPA-induced differentiation of HL60 cells towards monocytes. FEBS Lett. 1991 Jul 29;286(1-2):229–232. doi: 10.1016/0014-5793(91)80980-h. [DOI] [PubMed] [Google Scholar]
  21. Grafton G., Bunce C. M., Sheppard M. C., Brown G., Baxter M. A. Effect of Mg2+ on Na(+)-dependent inositol transport. Role for Mg2+ in etiology of diabetic complications. Diabetes. 1992 Jan;41(1):35–39. doi: 10.2337/diab.41.1.35. [DOI] [PubMed] [Google Scholar]
  22. Haye B., Champion S., Jacquemin C. Control by TSH of a phospholipase A 2 activity, a limiting factor in the biosynthesis of prostaglandins in the thyroid. FEBS Lett. 1973 Mar 15;30(3):253–260. doi: 10.1016/0014-5793(73)80664-7. [DOI] [PubMed] [Google Scholar]
  23. Haye B., Champion S., Jacquemin C. Existence of two pools of prostaglandins during stimulation of the thyroid by TSH. FEBS Lett. 1974 Apr 15;41(1):89–93. doi: 10.1016/0014-5793(74)80961-0. [DOI] [PubMed] [Google Scholar]
  24. Honda A., Morita I., Murota S., Mori Y. Appearance of the arachidonic acid metabolic pathway in human promyelocytic leukemia (HL-60) cells during monocytic differentiation: enhancement of thromboxane synthesis by 1 alpha,25-dihydroxyvitamin D-3. Biochim Biophys Acta. 1986 Jul 18;877(3):423–432. doi: 10.1016/0005-2760(86)90208-0. [DOI] [PubMed] [Google Scholar]
  25. Igarashi Y., Kondo Y. Transient increase in prostaglandin production as an acute response of thyroid isolated follicles to thyrotropin. Biochem Biophys Res Commun. 1981 Apr 30;99(4):1045–1050. doi: 10.1016/0006-291x(81)90724-5. [DOI] [PubMed] [Google Scholar]
  26. Imai A., Gershengorn M. C. Independent phosphatidylinositol synthesis in pituitary plasma membrane and endoplasmic reticulum. Nature. 1987 Feb 19;325(6106):726–728. doi: 10.1038/325726a0. [DOI] [PubMed] [Google Scholar]
  27. Khatami M., Rockey J. H. Regulation of uptake of inositol by glucose in cultured retinal pigment epithelial cells. Biochem Cell Biol. 1988 Sep;66(9):951–957. doi: 10.1139/o88-109. [DOI] [PubMed] [Google Scholar]
  28. Kwon H. M., Yamauchi A., Uchida S., Preston A. S., Garcia-Perez A., Burg M. B., Handler J. S. Cloning of the cDNa for a Na+/myo-inositol cotransporter, a hypertonicity stress protein. J Biol Chem. 1992 Mar 25;267(9):6297–6301. [PubMed] [Google Scholar]
  29. Mak W. W., Errick J. E., Chan R. C., Eggo M. C., Burrow G. N. Thyrotropin-induced formation of functional follicles in primary cultures of ovine thyroid cells. Exp Cell Res. 1986 Jun;164(2):311–322. doi: 10.1016/0014-4827(86)90031-5. [DOI] [PubMed] [Google Scholar]
  30. Marcocci C., Luini A., Santisteban P., Grollman E. F. Norepinephrine and thyrotropin stimulation of iodide efflux in FRTL-5 thyroid cells involves metabolites of arachidonic acid and is associated with the iodination of thyroglobulin. Endocrinology. 1987 Mar;120(3):1127–1133. doi: 10.1210/endo-120-3-1127. [DOI] [PubMed] [Google Scholar]
  31. Nakamura J., Del Monte M. A., Shewach D., Lattimer S. A., Greene D. A. Inhibition of phosphatidylinositol synthase by glucose in human retinal pigment epithelial cells. Am J Physiol. 1992 Apr;262(4 Pt 1):E417–E426. doi: 10.1152/ajpendo.1992.262.4.E417. [DOI] [PubMed] [Google Scholar]
  32. Pratt M. A., Eggo M. C., Bachrach L. K., Carayon P., Burrow G. N. Regulation of thyroperoxidase, thyroglobulin and iodide levels in sheep thyroid cells by TSH, tumor promoters and epidermal growth factor. Biochimie. 1989 Feb;71(2):227–235. doi: 10.1016/0300-9084(89)90060-6. [DOI] [PubMed] [Google Scholar]
  33. Reboulleau C. P. Inositol metabolism during neuroblastoma B50 cell differentiation: effects of differentiating agents on inositol uptake. J Neurochem. 1990 Aug;55(2):641–650. doi: 10.1111/j.1471-4159.1990.tb04181.x. [DOI] [PubMed] [Google Scholar]
  34. Saji M., Kohn L. D. 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. Endocrinology. 1991 Feb;128(2):1136–1143. doi: 10.1210/endo-128-2-1136. [DOI] [PubMed] [Google Scholar]
  35. Scott T. W., Mills S. C., Freinkel N. The mechanism of thyrotrophin action in relation to lipid metabolism in thyroid tissue. Biochem J. 1968 Sep;109(3):325–332. doi: 10.1042/bj1090325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sho K. M., Okajima F., Abdul Majid M., Kondo Y. Reciprocal modulation of thyrotropin actions by P1-purinergic agonists in FRTL-5 thyroid cells. Inhibition of cAMP pathway and stimulation of phospholipase C-Ca2+ pathway. J Biol Chem. 1991 Jul 5;266(19):12180–12184. [PubMed] [Google Scholar]
  37. Simmons D. A., Winegrad A. I., Martin D. B. Significance of tissue myo-inositol concentrations in metabolic regulation in nerve. Science. 1982 Aug 27;217(4562):848–851. doi: 10.1126/science.6285474. [DOI] [PubMed] [Google Scholar]
  38. Simmons D. A., Winegrad A. I. Mechanism of glucose-induced (Na+, K+)-ATPase inhibition in aortic wall of rabbits. Diabetologia. 1989 Jul;32(7):402–408. doi: 10.1007/BF00271258. [DOI] [PubMed] [Google Scholar]
  39. Stephens L. R., Jackson T. R., Hawkins P. T. Agonist-stimulated synthesis of phosphatidylinositol(3,4,5)-trisphosphate: a new intracellular signalling system? Biochim Biophys Acta. 1993 Oct 7;1179(1):27–75. doi: 10.1016/0167-4889(93)90072-w. [DOI] [PubMed] [Google Scholar]
  40. Tahara K., Grollman E. F., Saji M., Kohn L. D. Regulation of prostaglandin synthesis by thyrotropin, insulin or insulin-like growth factor-I, and serum in FRTL-5 rat thyroid cells. J Biol Chem. 1991 Jan 5;266(1):440–448. [PubMed] [Google Scholar]
  41. Tahara K., Saji M., Aloj S. M., Kohn L. D. The arachidonic acid signal system in the thyroid: regulation by thyrotropin and insulin/IGF-I. Adv Exp Med Biol. 1989;261:295–326. doi: 10.1007/978-1-4757-2058-7_12. [DOI] [PubMed] [Google Scholar]
  42. Takahashi S., Conti M., Prokop C., Van Wyk J. J., Earp H. S., 3rd Thyrotropin and insulin-like growth factor I regulation of tyrosine phosphorylation in FRTL-5 cells. Interaction between cAMP-dependent and growth factor-dependent signal transduction. J Biol Chem. 1991 Apr 25;266(12):7834–7841. [PubMed] [Google Scholar]
  43. Takasu N., Kubota T., Ujiie A., Hamano S., Yamada T., Shimizu Y. Augmentation of prostacyclin and depression of PGE2, PGF2 alpha and thromboxane A2 by TSH in cultured porcine thyroid cells: an important role of prostacyclin in maintaining thyroid cell function. FEBS Lett. 1981 Apr 20;126(2):301–305. doi: 10.1016/0014-5793(81)80266-9. [DOI] [PubMed] [Google Scholar]
  44. Wahl M. I., Nishibe S., Suh P. G., Rhee S. G., Carpenter G. Epidermal growth factor stimulates tyrosine phosphorylation of phospholipase C-II independently of receptor internalization and extracellular calcium. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1568–1572. doi: 10.1073/pnas.86.5.1568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Westermark K., Westermark B. Mitogenic effect of epidermal growth factor on sheep thyroid cells in culture. Exp Cell Res. 1982 Mar;138(1):47–55. doi: 10.1016/0014-4827(82)90089-1. [DOI] [PubMed] [Google Scholar]
  46. Wreggett K. A., Irvine R. F. A rapid separation method for inositol phosphates and their isomers. Biochem J. 1987 Aug 1;245(3):655–660. doi: 10.1042/bj2450655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Yorek M. A., Dunlap J. A., Ginsberg B. H. Myoinositol uptake by four cultured mammalian cell lines. Arch Biochem Biophys. 1986 May 1;246(2):801–807. doi: 10.1016/0003-9861(86)90336-x. [DOI] [PubMed] [Google Scholar]
  48. Yu S. C., Chang L., Burke G. Thyrotropin increases prostaglandin levels in isolated thyroid cells. J Clin Invest. 1972 Apr;51(4):1038–1042. doi: 10.1172/JCI106864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Zhu X., Eichberg J. A myo-inositol pool utilized for phosphatidylinositol synthesis is depleted in sciatic nerve from rats with streptozotocin-induced diabetes. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9818–9822. doi: 10.1073/pnas.87.24.9818. [DOI] [PMC free article] [PubMed] [Google Scholar]

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