Abstract
Previous findings from our laboratory have shown that pituitary calcitonin-like peptide (pit-CT) is synthesized and released by gonadotrophs and inhibits prolactin (PRL) release, synthesis, and lactotroph proliferation. To investigate further the regulation of PRL gene transcription by CT, we examined the effect of CT on rat PRL (rPRL) promoter activity in rat pituitary GGH3 cells. GGH3 cells were transiently transfected with rPRL promoter-luciferase and control plasmids. Thirty-six hours later, the cells were treated with CT or other agents and their effect on luciferase activity was examined. The effect of CT and/or thyrotropin-releasing hormone (TRH) on p42/44 mitogen-activated protein kinase (MAPK) activity was also investigated. CT inhibited basal rPRL promoter activity in a dose-dependent fashion, with an approximate IC50 of 3 nM. The maximal inhibition occurred 1 h after the CT addition, and the peptide was equipotent in inhibiting −600 and −2500 rPRL promoter constructs. CT also inhibited TRH-, Bay K 8644-, and ionomycin-induced rPRL promoter activity. CT mimicked the actions of MEK inhibitors U0126 and PD 980089. However, CT could not inhibit rPRL promoter activity in GGH3 cells expressing constitutively active ERK1 or ERK2. CT markedly attenuated phospho-MAPK immunoreactivity in untreated as well as TRH-treated GGH3 cells. These results suggest that CT inhibits rPRL promoter activity by antagonizing Ca2+ and ERK1/2-mediated signaling events. They also demonstrate that CT is a potent inhibitor of early events associated with PRL gene activation and may play an important role in regulation of lactotroph function.
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References
Azria, M. (1989). The calcitonins. Karger: Basel.
Fischer, J. A. and Born, W. (1985). Peptides 6(Suppl. 3), 265–271.
Potts, J. T. Jr. (1976). In: Handbook of physiology. Aurbach, G. D. (ed.). American Physiological Society: Washington, DC.
Stevenson, J. C. (1980). Invest. Cell Pathol. 3, 187–193.
Fischer, J. A., Tobler, P. H., Kaufmann, M., et al. (1981). Proc. Natl. Acad. Sci. USA 78, 7801–7805.
Flynn, J. J., Margules, D. L., and Cooper, C. W. (1981). Brain Res. Bull. 6(6), 547–549.
Sexton, P. M. and Hilton, J. M. (1992). Brain Res. 596, 279–284.
Hilton, J. M., Mitchelhill, K. I., Pozvek, G., Dowton, M., Quiza, M., and Sexton, P. M. (1998). Endocrinology 139(3), 982–992.
Shah, G. V., Deftos, L. J., and Crowley, W. R. (1993). Endocrinology 132(3), 1367–1372.
Gropp, C., Luster, W., and Havemann, K. (1985). Br. J. Cancer 51, 897–901.
Zhu, L. J., Cullinan-Bove, K., Polihronis, M., Bagchi, M. K., and Bagchi, I. C. (1998). Endocrinology 139, 3923–3934.
Rizzo, A. J. and Goltzman, D. (1981). Endocrinology 108, 1672–1677.
Wang, J., Rout, U. K., Bagchi, I. C., and Armant, D. R. (1998). Development 125(21), 4293–4302.
Chien, J., Ren, Y., Wong, Y. Q., et al. (2001). Mol. Cell Endocrinol. 181, 69–79.
Albrandt, K., Mull, E., Brady, E. M., Herich, J., Moore, C. X., and Beaumont, K. (1993). FEBS Lett. 325, 225–232.
Clementi, G., Nicoletti, F., Patacchioli, F., et al. (1983). J. Neurochem. 40(3), 885, 886.
Franceschini, R., Cataldi, R. A., Cianciosi, P., et al. (1993). Biomed. Pharmacother. 47(8), 305–309.
Freed, W. J., Perlow, M. J., and Wyatt, R. J. (1979). Science 206, 850–852.
Judd, A. M., Kubota, T., Kuan, S. I., Jarvis, W. D., Spangelo, B. L., and MacLeod, R. M. (1990). Endocrinology 127, 191–199.
Chronwall, B. M., Sands, S. A., Li, Z., and Shah, G. V. (1996). Endocrine 4, 27–33.
Ren, Y., Chien, J., Sun, Y. P., and Shah, G. V. (2001). J. Endocrinol. 171, 217–228.
Shah, G. V., Wang, W., Grosvenor, C. E., and Crowley, W. R. (1990). Endocrinology 132, 621–628.
Zhang, Q., Stanley, S., and Shah, G. V. (1995). Endocrine 3, 445–451.
Shah, G. V., Chien, J., Sun, Y. P., Puri, S., and Ravindra, R. (1999). Endocrinology 140, 4281–4291.
Sun, Y. P., Ren, Y., Lee, T. J., and Shah, G. V. (2002). Endocrinology 143, 4056–4064.
Harvey, C., Jackson, S. M., Siddiqui, S. K., and Gutierrez Hartmann, A. (1991). Mol. Endocrinol. 5, 836–843.
Iverson, R. A., Day, K. H., d’Emden, M., Day, R. N., and Maurer, R. A. (1990). Mol. Endocrinol. 4, 1564–1571.
Sexton, P. M., Houssami, S., Hilton, J. M., et al. (1993). Mol. Endocrinol. 7(6), 815–821.
Wang, Y. H. and Maurer, R. A. (1999). Mol. Endocrinol. 13(7), 1094–1104.
Shah, G. V., Epand, R. M., and Orlowsky, R. C. (1988). J. Endocrinol. 116, 279–286.
Shah, G. V., Pedchenko, V., Stanley, S., Li, Z., and Samson, W. K. (1996). Endocrinology 137(5), 1814–1822.
Day, R. N. and Maurer, R. A. (1990). Mol. Endocrinol. 4, 736–742.
Enyeart, J. J., Biagi, B. A., Day, R. N., Sheu, S. S., and Maurer, R. A. (1990). J. Biol. Chem. 265, 16,373–16,379.
Day, R. N., Walder, J. A., and Maurer, R. A. (1989). J. Biol. Chem. 264, 431–436.
Nowakowski, B. E., Okimura, Y., and Maurer, R. A. (1997). Mol. Cell Endocrinol. 132(1–2), 109–116.
Albert, P. R. and Tashjian, A. H. J. (1984). J. Biol. Chem. 259, 15350–15363.
Albert, P. R. and Tashjian, A. H. J. (1985). J. Biol. Chem. 260, 8746–8759.
Aub, D. L., Frey, E. A., Sekura, R. D., and Cote, T. E. (1986). J. Biol. Chem. 261, 9333–9340.
Gershengorn, M. C. and Thaw, C. (1985). Endocrinology 116, 591–596.
Shah, G. V., Kennedy, D., Dockter, M. E., and Crowley, W. R. (1990). Endocrinology 127, 613–620.
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Ren, Y., Sun, YP. & Shah, G.V. Calcitonin inhibits prolactin promoter activity in rat pituitary GGH3 cells. Endocr 20, 13–21 (2003). https://doi.org/10.1385/ENDO:20:1-2:13
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DOI: https://doi.org/10.1385/ENDO:20:1-2:13