Skip to main content
Log in

Calcitonin inhibits prolactin promoter activity in rat pituitary GGH3 cells

Evidence for involvement of p42/44 mitogen-activated protein kinase in calcitonin action

  • Published:
Endocrine Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Azria, M. (1989). The calcitonins. Karger: Basel.

    Google Scholar 

  2. Fischer, J. A. and Born, W. (1985). Peptides 6(Suppl. 3), 265–271.

    Article  PubMed  CAS  Google Scholar 

  3. Potts, J. T. Jr. (1976). In: Handbook of physiology. Aurbach, G. D. (ed.). American Physiological Society: Washington, DC.

    Google Scholar 

  4. Stevenson, J. C. (1980). Invest. Cell Pathol. 3, 187–193.

    PubMed  CAS  Google Scholar 

  5. Fischer, J. A., Tobler, P. H., Kaufmann, M., et al. (1981). Proc. Natl. Acad. Sci. USA 78, 7801–7805.

    Article  PubMed  CAS  Google Scholar 

  6. Flynn, J. J., Margules, D. L., and Cooper, C. W. (1981). Brain Res. Bull. 6(6), 547–549.

    Article  PubMed  CAS  Google Scholar 

  7. Sexton, P. M. and Hilton, J. M. (1992). Brain Res. 596, 279–284.

    Article  PubMed  CAS  Google Scholar 

  8. Hilton, J. M., Mitchelhill, K. I., Pozvek, G., Dowton, M., Quiza, M., and Sexton, P. M. (1998). Endocrinology 139(3), 982–992.

    Article  PubMed  CAS  Google Scholar 

  9. Shah, G. V., Deftos, L. J., and Crowley, W. R. (1993). Endocrinology 132(3), 1367–1372.

    Article  PubMed  CAS  Google Scholar 

  10. Gropp, C., Luster, W., and Havemann, K. (1985). Br. J. Cancer 51, 897–901.

    PubMed  CAS  Google Scholar 

  11. Zhu, L. J., Cullinan-Bove, K., Polihronis, M., Bagchi, M. K., and Bagchi, I. C. (1998). Endocrinology 139, 3923–3934.

    Article  PubMed  CAS  Google Scholar 

  12. Rizzo, A. J. and Goltzman, D. (1981). Endocrinology 108, 1672–1677.

    PubMed  CAS  Google Scholar 

  13. Wang, J., Rout, U. K., Bagchi, I. C., and Armant, D. R. (1998). Development 125(21), 4293–4302.

    PubMed  CAS  Google Scholar 

  14. Chien, J., Ren, Y., Wong, Y. Q., et al. (2001). Mol. Cell Endocrinol. 181, 69–79.

    Article  PubMed  CAS  Google Scholar 

  15. Albrandt, K., Mull, E., Brady, E. M., Herich, J., Moore, C. X., and Beaumont, K. (1993). FEBS Lett. 325, 225–232.

    Article  PubMed  CAS  Google Scholar 

  16. Clementi, G., Nicoletti, F., Patacchioli, F., et al. (1983). J. Neurochem. 40(3), 885, 886.

    Article  PubMed  CAS  Google Scholar 

  17. Franceschini, R., Cataldi, R. A., Cianciosi, P., et al. (1993). Biomed. Pharmacother. 47(8), 305–309.

    Article  PubMed  CAS  Google Scholar 

  18. Freed, W. J., Perlow, M. J., and Wyatt, R. J. (1979). Science 206, 850–852.

    Article  PubMed  CAS  Google Scholar 

  19. Judd, A. M., Kubota, T., Kuan, S. I., Jarvis, W. D., Spangelo, B. L., and MacLeod, R. M. (1990). Endocrinology 127, 191–199.

    PubMed  CAS  Google Scholar 

  20. Chronwall, B. M., Sands, S. A., Li, Z., and Shah, G. V. (1996). Endocrine 4, 27–33.

    Article  CAS  Google Scholar 

  21. Ren, Y., Chien, J., Sun, Y. P., and Shah, G. V. (2001). J. Endocrinol. 171, 217–228.

    Article  PubMed  CAS  Google Scholar 

  22. Shah, G. V., Wang, W., Grosvenor, C. E., and Crowley, W. R. (1990). Endocrinology 132, 621–628.

    Article  Google Scholar 

  23. Zhang, Q., Stanley, S., and Shah, G. V. (1995). Endocrine 3, 445–451.

    Article  Google Scholar 

  24. Shah, G. V., Chien, J., Sun, Y. P., Puri, S., and Ravindra, R. (1999). Endocrinology 140, 4281–4291.

    Article  PubMed  CAS  Google Scholar 

  25. Sun, Y. P., Ren, Y., Lee, T. J., and Shah, G. V. (2002). Endocrinology 143, 4056–4064.

    Article  PubMed  CAS  Google Scholar 

  26. Harvey, C., Jackson, S. M., Siddiqui, S. K., and Gutierrez Hartmann, A. (1991). Mol. Endocrinol. 5, 836–843.

    PubMed  CAS  Google Scholar 

  27. Iverson, R. A., Day, K. H., d’Emden, M., Day, R. N., and Maurer, R. A. (1990). Mol. Endocrinol. 4, 1564–1571.

    PubMed  CAS  Google Scholar 

  28. Sexton, P. M., Houssami, S., Hilton, J. M., et al. (1993). Mol. Endocrinol. 7(6), 815–821.

    Article  PubMed  CAS  Google Scholar 

  29. Wang, Y. H. and Maurer, R. A. (1999). Mol. Endocrinol. 13(7), 1094–1104.

    Article  PubMed  CAS  Google Scholar 

  30. Shah, G. V., Epand, R. M., and Orlowsky, R. C. (1988). J. Endocrinol. 116, 279–286.

    Article  PubMed  CAS  Google Scholar 

  31. Shah, G. V., Pedchenko, V., Stanley, S., Li, Z., and Samson, W. K. (1996). Endocrinology 137(5), 1814–1822.

    Article  PubMed  CAS  Google Scholar 

  32. Day, R. N. and Maurer, R. A. (1990). Mol. Endocrinol. 4, 736–742.

    PubMed  CAS  Google Scholar 

  33. 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.

    CAS  Google Scholar 

  34. Day, R. N., Walder, J. A., and Maurer, R. A. (1989). J. Biol. Chem. 264, 431–436.

    PubMed  CAS  Google Scholar 

  35. Nowakowski, B. E., Okimura, Y., and Maurer, R. A. (1997). Mol. Cell Endocrinol. 132(1–2), 109–116.

    Article  PubMed  CAS  Google Scholar 

  36. Albert, P. R. and Tashjian, A. H. J. (1984). J. Biol. Chem. 259, 15350–15363.

    PubMed  CAS  Google Scholar 

  37. Albert, P. R. and Tashjian, A. H. J. (1985). J. Biol. Chem. 260, 8746–8759.

    PubMed  CAS  Google Scholar 

  38. Aub, D. L., Frey, E. A., Sekura, R. D., and Cote, T. E. (1986). J. Biol. Chem. 261, 9333–9340.

    PubMed  CAS  Google Scholar 

  39. Gershengorn, M. C. and Thaw, C. (1985). Endocrinology 116, 591–596.

    PubMed  CAS  Google Scholar 

  40. Shah, G. V., Kennedy, D., Dockter, M. E., and Crowley, W. R. (1990). Endocrinology 127, 613–620.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Girish V. Shah.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/ENDO:20:1-2:13

Key Words

Navigation