Abstract
Studies were conducted to determine whether thyroid-stimulating hormone (TSH; thyrotropin), a hormone known to increase cytosol concentrations of cyclic AMP, also stimulates the formation of inositol phosphates in thyroid cells. TSH and noradrenaline both stimulated [3H]inositol phosphate formation in a concentration-dependent manner in the rat thyroid cell line, FRTL-5 cells, which had been prelabelled with [3H]inositol. The threshold concentration of TSH required to stimulate inositol phosphate formation was more than 20 munits/ml, which is approx. 10(3)-fold greater than that required for cyclic AMP accumulation and growth in these cells. We also demonstrate that membranes prepared from FRTL-5 cells possess a guanine nucleotide-activatable polyphosphoinositide phosphodiesterase, which suggests that activation of inositide metabolism in these cells may be coupled to receptors by the G-protein, Gp. Our findings suggest that two second-messenger systems exist to mediate the action of TSH in the thyroid.
Full text
PDF![519](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfde/1148444/3bfe616d14c3/biochemj00244-0031.png)
![520](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfde/1148444/fc966e843d61/biochemj00244-0032.png)
![521](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfde/1148444/79f182fda0ea/biochemj00244-0033.png)
![522](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfde/1148444/2a945f0e8fea/biochemj00244-0034.png)
![523](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfde/1148444/34079faeaef6/biochemj00244-0035.png)
![524](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfde/1148444/13d77f74c9ff/biochemj00244-0036.png)
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ambesi-Impiombato F. S., Parks L. A., Coon H. G. Culture of hormone-dependent functional epithelial cells from rat thyroids. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3455–3459. doi: 10.1073/pnas.77.6.3455. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barrowman M. M., Cockcroft S., Gomperts B. D. Differential control of azurophilic and specific granule exocytosis in Sendai-virus-permeabilized rabbit neutrophils. J Physiol. 1987 Feb;383:115–124. doi: 10.1113/jphysiol.1987.sp016399. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bennett N., Dupont Y. The G-protein of retinal rod outer segments (transducin). Mechanism of interaction with rhodopsin and nucleotides. J Biol Chem. 1985 Apr 10;260(7):4156–4168. [PubMed] [Google Scholar]
- Berridge M. J., Dawson R. M., Downes C. P., Heslop J. P., Irvine R. F. Changes in the levels of inositol phosphates after agonist-dependent hydrolysis of membrane phosphoinositides. Biochem J. 1983 May 15;212(2):473–482. doi: 10.1042/bj2120473. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berridge M. J., Downes C. P., Hanley M. R. Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands. Biochem J. 1982 Sep 15;206(3):587–595. doi: 10.1042/bj2060587. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berridge M. J. Ernst Klenk Lecture, November 1985. Intracellular signalling through inositol trisphosphate and diacylglycerol. Biol Chem Hoppe Seyler. 1986 Jun;367(6):447–456. [PubMed] [Google Scholar]
- Berridge M. J., Heslop J. P. Separate 5-hydroxytryptamine receptors on the salivary gland of the blowfly are linked to the generation of either cyclic adenosine 3',5'-monophosphate or calcium signals. Br J Pharmacol. 1981 Jul;73(3):729–738. doi: 10.1111/j.1476-5381.1981.tb16809.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
- Bidey S. P., Chiovato L., Day A., Turmaine M., Gould R. P., Ekins R. P., Marshall N. J. Evaluation of the rat thyroid cell strain FRTL-5 as an in-vitro bioassay system for thyrotrophin. J Endocrinol. 1984 Jun;101(3):269–276. doi: 10.1677/joe.0.1010269. [DOI] [PubMed] [Google Scholar]
- Burch R. M., Luini A., Axelrod J. Phospholipase A2 and phospholipase C are activated by distinct GTP-binding proteins in response to alpha 1-adrenergic stimulation in FRTL5 thyroid cells. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7201–7205. doi: 10.1073/pnas.83.19.7201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cockcroft S., Gomperts B. D. Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase. Nature. 1985 Apr 11;314(6011):534–536. doi: 10.1038/314534a0. [DOI] [PubMed] [Google Scholar]
- Cockcroft S., Taylor J. A. Fluoroaluminates mimic guanosine 5'-[gamma-thio]triphosphate in activating the polyphosphoinositide phosphodiesterase of hepatocyte membranes. Role for the guanine nucleotide regulatory protein Gp in signal transduction. Biochem J. 1987 Jan 15;241(2):409–414. doi: 10.1042/bj2410409. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cockcroft S., Taylor J. A., Judah J. D. Subcellular localisation of inositol lipid kinases in rat liver. Biochim Biophys Acta. 1985 May 30;845(2):163–170. doi: 10.1016/0167-4889(85)90173-9. [DOI] [PubMed] [Google Scholar]
- Cockcroft S. The dependence on Ca2+ of the guanine-nucleotide-activated polyphosphoinositide phosphodiesterase in neutrophil plasma membranes. Biochem J. 1986 Dec 1;240(2):503–507. doi: 10.1042/bj2400503. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Corda D., Marcocci C., Kohn L. D., Axelrod J., Luini A. Association of the changes in cytosolic Ca2+ and iodide efflux induced by thyrotropin and by the stimulation of alpha 1-adrenergic receptors in cultured rat thyroid cells. J Biol Chem. 1985 Aug 5;260(16):9230–9236. [PubMed] [Google Scholar]
- Davis J. S., Weakland L. L., West L. A., Farese R. V. Luteinizing hormone stimulates the formation of inositol trisphosphate and cyclic AMP in rat granulosa cells. Evidence for phospholipase C generated second messengers in the action of luteinizing hormone. Biochem J. 1986 Sep 1;238(2):597–604. doi: 10.1042/bj2380597. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Downes C. P., Hawkins P. T., Irvine R. F. Inositol 1,3,4,5-tetrakisphosphate and not phosphatidylinositol 3,4-bisphosphate is the probable precursor of inositol 1,3,4-trisphosphate in agonist-stimulated parotid gland. Biochem J. 1986 Sep 1;238(2):501–506. doi: 10.1042/bj2380501. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Downes C. P., Mussat M. C., Michell R. H. The inositol trisphosphate phosphomonoesterase of the human erythrocyte membrane. Biochem J. 1982 Apr 1;203(1):169–177. doi: 10.1042/bj2030169. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ealey P. A., Emmerson J. M., Bidey S. P., Marshall N. J. Thyrotrophin stimulation of mitogenesis of the rat thyroid cell strain FRTL-5: a metaphase index assay for the detection of thyroid growth stimulators. J Endocrinol. 1985 Aug;106(2):203–210. doi: 10.1677/joe.0.1060203. [DOI] [PubMed] [Google Scholar]
- FREINKEL N. Pathways of thyroidal phosphorus metabolism: the effect of pituitary thyrotropin upon the phospholipids of the sheep thyroid gland. Endocrinology. 1957 Oct;61(4):448–460. doi: 10.1210/endo-61-4-448. [DOI] [PubMed] [Google Scholar]
- Farese R. V., Rosic N., Babischkin J., Farese M. G., Foster R., Davis J. S. Dual activation of the inositol-triphosphate-calcium and cyclic nucleotide intracellular signaling systems by adrenocorticotropin in rat adrenal cells. Biochem Biophys Res Commun. 1986 Mar 28;135(3):742–748. doi: 10.1016/0006-291x(86)90991-5. [DOI] [PubMed] [Google Scholar]
- Field J. B. Thyroid-stimulating hormone and cyclic adenosine 3',5'-monophosphate in the regulation of thyroid gland function. Metabolism. 1975 Mar;24(3):381–393. doi: 10.1016/0026-0495(75)90118-3. [DOI] [PubMed] [Google Scholar]
- Gilman A. G. G proteins and dual control of adenylate cyclase. Cell. 1984 Mar;36(3):577–579. doi: 10.1016/0092-8674(84)90336-2. [DOI] [PubMed] [Google Scholar]
- Hawkins P. T., Stephens L., Downes C. P. Rapid formation of inositol 1,3,4,5-tetrakisphosphate and inositol 1,3,4-trisphosphate in rat parotid glands may both result indirectly from receptor-stimulated release of inositol 1,4,5-trisphosphate from phosphatidylinositol 4,5-bisphosphate. Biochem J. 1986 Sep 1;238(2):507–516. doi: 10.1042/bj2380507. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haye B., Jacquemin C. Stimulation par la thyréostimuline de la production de l'inositol 1-2 phosphate cyclique. Biochimie. 1974;56(9):1283–1285. doi: 10.1016/s0300-9084(74)80022-2. [DOI] [PubMed] [Google Scholar]
- Hirayu H., Magnusson R. P., Rapoport B. Studies on the mechanism of desensitization of the cyclic AMP response to TSH stimulation in a cloned rat thyroid cell line. Mol Cell Endocrinol. 1985 Aug;42(1):21–27. doi: 10.1016/0303-7207(85)90003-6. [DOI] [PubMed] [Google Scholar]
- Igarashi Y., Kondo Y. Acute effect of thyrotropin on phosphatidylinositol degradation and transient accumulation of diacylglycerol in isolated thyroid follicles. Biochem Biophys Res Commun. 1980 Nov 28;97(2):759–765. doi: 10.1016/0006-291x(80)90329-0. [DOI] [PubMed] [Google Scholar]
- Irvine R. F. How is the level of free arachidonic acid controlled in mammalian cells? Biochem J. 1982 Apr 15;204(1):3–16. doi: 10.1042/bj2040003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kotani M., Kariya T., Field J. B. Studies of thyroid-stimulating hormone binding to bovine thyroid plasma membranes. Metabolism. 1975 Aug;24(8):959–971. doi: 10.1016/0026-0495(75)90088-8. [DOI] [PubMed] [Google Scholar]
- MORTON M. E., SCHWARTZ J. R. The stimulation in vitro of phospholipid synthesis in thyroid tissue by thyrotrophic hormone. Science. 1953 Jan 30;117(3031):103–104. doi: 10.1126/science.117.3031.103. [DOI] [PubMed] [Google Scholar]
- Manley S. W., Bourke J. R., Hawker R. W. Reversible binding of labelled and non-labelled thyrotrophin by intact thyroid tissue in vitro. J Endocrinol. 1972 Dec;55(3):555–563. doi: 10.1677/joe.0.0550555. [DOI] [PubMed] [Google Scholar]
- Martin T. F., Lucas D. O., Bajjalieh S. M., Kowalchyk J. A. Thyrotropin-releasing hormone activates a Ca2+-dependent polyphosphoinositide phosphodiesterase in permeable GH3 cells. GTP gamma S potentiation by a cholera and pertussis toxin-insensitive mechanism. J Biol Chem. 1986 Feb 25;261(6):2918–2927. [PubMed] [Google Scholar]
- Nambi P., Peters J. R., Sibley D. R., Lefkowitz R. J. Desensitization of the turkey erythrocyte beta-adrenergic receptor in a cell-free system. Evidence that multiple protein kinases can phosphorylate and desensitize the receptor. J Biol Chem. 1985 Feb 25;260(4):2165–2171. [PubMed] [Google Scholar]
- Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
- Philp N. J., Grollman E. F. Thyrotropin and norepinephrine stimulate the metabolism of phosphoinositides in FRTL-5 thyroid cells. FEBS Lett. 1986 Jul 7;202(2):193–196. doi: 10.1016/0014-5793(86)80685-8. [DOI] [PubMed] [Google Scholar]
- Piot J. M., Jacquemin C. Lack of adenylate and guanylate cyclases responsiveness to hormones in a spontaneous murine thyroid tumor. Biochem Biophys Res Commun. 1980 Jul 16;95(1):357–366. doi: 10.1016/0006-291x(80)90746-9. [DOI] [PubMed] [Google Scholar]
- Rebois R. V., Patel J. Phorbol ester causes desensitization of gonadotropin-responsive adenylate cyclase in a murine Leydig tumor cell line. J Biol Chem. 1985 Jul 5;260(13):8026–8031. [PubMed] [Google Scholar]
- Scott T. W., Freinkel N., Klein J. H., Nitzan M. Metabolism of phospholipids, neutral lipids and carbohydrates in dispersed porcine thyroid cells: comparative effects of pituitary thyrotropin and dibutyryl-3',5'-adenosine monophosphate on the turnover of slices from pig thyroid. Endocrinology. 1970 Nov;87(5):854–863. doi: 10.1210/endo-87-5-854. [DOI] [PubMed] [Google Scholar]
- 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]
- Smith B. R., Hall R. Binding of thyroid stimulators to thyroid membranes. FEBS Lett. 1974 Jun 15;42(3):301–304. doi: 10.1016/0014-5793(74)80751-9. [DOI] [PubMed] [Google Scholar]
- Tramontano D., Ingbar S. H. Properties and regulation of the thyrotropin receptor in the FRTL5 rat thyroid cell line. Endocrinology. 1986 May;118(5):1945–1951. doi: 10.1210/endo-118-5-1945. [DOI] [PubMed] [Google Scholar]
- Trimble E. R., Bruzzone R., Biden T. J., Farese R. V. Secretin induces rapid increases in inositol trisphosphate, cytosolic Ca2+ and diacylglycerol as well as cyclic AMP in rat pancreatic acini. Biochem J. 1986 Oct 15;239(2):257–261. doi: 10.1042/bj2390257. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Uhing R. J., Prpic V., Jiang H., Exton J. H. Hormone-stimulated polyphosphoinositide breakdown in rat liver plasma membranes. Roles of guanine nucleotides and calcium. J Biol Chem. 1986 Feb 15;261(5):2140–2146. [PubMed] [Google Scholar]
- Verrier B., Fayet G., Lissitzky S. Thyrotropin-binding properties of isolated thyroid cells and their purified plasma membranes. Relation of thyrotropin-specific binding to adenylate-cyclase activation. Eur J Biochem. 1974 Mar 1;42(2):355–365. doi: 10.1111/j.1432-1033.1974.tb03347.x. [DOI] [PubMed] [Google Scholar]
- Wakelam M. J., Murphy G. J., Hruby V. J., Houslay M. D. Activation of two signal-transduction systems in hepatocytes by glucagon. Nature. 1986 Sep 4;323(6083):68–71. doi: 10.1038/323068a0. [DOI] [PubMed] [Google Scholar]
- Zor U., Lowe I. P., Bloom G., Field J. B. The role of calcium (Ca++) in TSH and dibutyryl 3'5' cyclic AMP stimulation of thyroid glucose oxidation and phospholipid synthesis. Biochem Biophys Res Commun. 1968 Nov 25;33(4):649–658. doi: 10.1016/0006-291x(68)90345-8. [DOI] [PubMed] [Google Scholar]