, Volume 13, Issue 1, pp 11–15 | Cite as

Interleukin-6 regulation of kappa opioid receptor gene expression in primary sertoli cells



Three classes of opioid receptors—mu, delta, and kappa—mediate physiological and pharmacological functions of the endogenous opioid peptides and exogenous opioid compounds in the central nervous system (CNS), as well as in peripheral tissues including the immune system. Using reverse transcriptase polymerase chain reaction (RT-PCR) analysis, we show that freshly isolated and highly purified somatic (Sertoli and Leydig) and specific germ (spermatogonia, pachytene spermatocytes, round, and elongating spermatids) cells of the rat testis differentially express the mRNAs for these opioid receptor genes. Furthermore, to identify a functional mechanism for cytokine regulation of testicular opioid receptor gene expression, we employed primary Sertoli cells as a model system. In a semiquantitative PCR analysis using the S16 ribosomal RNA gene as an internal control, we show that interleukin-6 reduces kappa opioid receptor mRNA levels from 6 to 24 h of treatment in primary Sertoli cells. This regulation requires new RNA and protein synthesis and is partially mediated by the protein kinase A pathway. These findings are consistent with a role for the cytokine and opioid signaling pathways in Sertoli cellular function and the interaction that exists between the opioid and the immune systems in the CNS.

Key Words

Opioid receptor, subtypes Sertoli Leydig male germ cells protein kinase A 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Goldstein, A. (1987). Trends Pharmacol. Sci. 8, 456–459.CrossRefGoogle Scholar
  2. 2.
    Pasternak, G. W. (1993). Clin. Neuropharmacol. 16, 1–18.PubMedCrossRefGoogle Scholar
  3. 3.
    Wittert, G., Hope, P., and Pyle, D. (1996). Biochem. Biophys. Res. Commun. 218, 877–881.PubMedCrossRefGoogle Scholar
  4. 4.
    Tian, M., Broxmeyer, H. E., Fan, Y., Lai, Z., Zhang, S., Aronica, S., Cooper, S., Bigsby, R. M., Steinmetz, R., Engle, S. J., Mestek, A., Pollock, J. D., Lehman, M. N., Jansen, H. T., Ying, M., Stambrook, P. J., Tischfield, J. A., and Yu, L. (1997). J. Exp. Med. 185, 1517–1522.PubMedCrossRefGoogle Scholar
  5. 5.
    Brown, S. L., Smith, L. R., and Blalock, J. E. (1987). J. Immunol. 139, 3181–3183.PubMedGoogle Scholar
  6. 6.
    Chuang, L. F., Chuang, T. K., Killam, K. F., Chuang, A. J., Kung, H. F., Yu, L., and Chuang, R. Y. (1994). Biochem. Biophys. Res. Commun. 202, 1291–1299.PubMedCrossRefGoogle Scholar
  7. 7.
    Ruzicka, B. B. and Akil, H. (1997). Neuroscience 79, 517–524.PubMedCrossRefGoogle Scholar
  8. 8.
    Ruzicka, B. B., Thompson, R. C., Waton, S. J., and Akil, H. (1996). J. Neurochem. 66, 425–428.PubMedCrossRefGoogle Scholar
  9. 9.
    Ihle, J. N. and Kerr, I. M. (1995). Trends Genet. 11, 69–74.PubMedCrossRefGoogle Scholar
  10. 10.
    Kishimoto, T., Taga, T., and Akira, S. (1994). Cell 76, 253–262.PubMedCrossRefGoogle Scholar
  11. 11.
    Darnell, J. E. Jr., Kerr, I. M., and Stark, G. R. (1994). Science 264, 1415–1420.PubMedCrossRefGoogle Scholar
  12. 12.
    Wagner, B. J., Hayes, T. E., Hoban, C. J., and Cochran, H. (1990). EMBO J. 9, 4477–4484.PubMedGoogle Scholar
  13. 13.
    Nakajima, K. and Wall, R. (1991). Mol. Cell. Biol. 11, 1409–1418.PubMedGoogle Scholar
  14. 14.
    Coffer, P., Lutticken, C., van Puijenbroek, A., Klop-de Jonge, M., Horn, F., and Kruijer, W. (1995). Oncogene 10, 985–994.PubMedGoogle Scholar
  15. 15.
    Jenab, S. and Morris, P. L. (1996). Endocrinology 137, 4738–4743.PubMedCrossRefGoogle Scholar
  16. 16.
    Jenab, S and Morris, P. L. (1997). Endocrinology 138, 2740–2746.PubMedCrossRefGoogle Scholar
  17. 17.
    Okuda, Y., Sun, X. R., and Morris, P. L. (1994). Endocrine 2, 617–624.Google Scholar
  18. 18.
    Okuda, Y. and Morris, P. L. (1994). Endocrine 2, 1163–1168.Google Scholar
  19. 19.
    Fujisawa, M., Bardin, C. W., and Morris, P. L. (1992). Mol. Cell. Endocrinol. 84, 79–88.PubMedCrossRefGoogle Scholar
  20. 20.
    Kew, D. and Kilpatrick, D. L. (1989). Mol. Endocrinol. 3, 179–184.PubMedGoogle Scholar
  21. 21.
    Kilpatrick, D. L., Borland, K., and Jin, D. F. (1987). Proc. Natl. Acad. Sci. USA 84, 5695–5699.PubMedCrossRefGoogle Scholar
  22. 22.
    Morris, P. L., Vale, W. W., and Bardin, C. W. (1987). Biochem. Biphys. Res. Commun. 148, 1513–1519.CrossRefGoogle Scholar
  23. 23.
    Jenab, S, Kest, B., Franklin, S. O., and Inturrisi, C. E. (1995). Life Sci. 56, 2343–2355.PubMedCrossRefGoogle Scholar
  24. 24.
    Brodsky, M., Elliott, K. J., Hynasky, A., Jenab, S, and Inturrisi, C. E. (1995). Neuroreport 6, 725–729.PubMedCrossRefGoogle Scholar
  25. 25.
    Day, H. E. W. and Akil, H. (1996). Neuroendocrinol. 63, 207–218.Google Scholar
  26. 26.
    Curran, T. and Franza, R. B. Jr., (1998). Cell 55, 395–397.CrossRefGoogle Scholar
  27. 27.
    Chiu, R., Angel, P., and Karin, M. (1989). Cell 59, 979–986.PubMedCrossRefGoogle Scholar
  28. 28.
    Schutte, J., Viallet, J., Nau, M., Segal, S., Fedorko, J., and Minna, J. (1989). Cell 59, 987–997.PubMedCrossRefGoogle Scholar
  29. 29.
    Beczkowska, I. W., Buck, J., and Inturrisi, C. E. (1996). Brain Res. Bull. 39, 193–199.PubMedCrossRefGoogle Scholar
  30. 30.
    Rahmsdorf, H. J., Schonthal, A., Angel, P., Litfin, M., Ruther, U., and Herrlich, P. (1987). Nucleic Acids Res. 15, 1643–1659.PubMedCrossRefGoogle Scholar
  31. 31.
    Greenberg, M. E., Hermanowski, A. L., and Ziff, E. B. (1986). Mol. Cell Biol. 6, 1050–1057.PubMedGoogle Scholar
  32. 32.
    Jenab, S. and Inturrisi, C. E. (1994). Mol. Brain Res. 27, 95–102.PubMedCrossRefGoogle Scholar
  33. 33.
    Jenab, S. and Inturrisi, C. E. (1997). Mol. Brain Res. 47, 44–48.PubMedCrossRefGoogle Scholar
  34. 34.
    Andersson, K. B., Tasken, K., and Blomhoff, H. K. (1994). FEBS Lett. 337, 71–76.PubMedCrossRefGoogle Scholar
  35. 35.
    Yoshikawa, K. and Sabol, S. L. (1986). Biochem. Biophys. Res. Commun. 139, 1–10.PubMedCrossRefGoogle Scholar
  36. 36.
    Jenab, S. and Inturrisi, C. E. (1995). Biochem. Biophys. Res. Commun. 210, 589–599.PubMedCrossRefGoogle Scholar
  37. 37.
    Collard, M. W., Day, R., Akil, H., Uhler, M. D., and Douglass, J. O. (1990). Mol. Endocrinol. 4, 1488–1496.PubMedGoogle Scholar
  38. 38.
    Gagner, J. P. and Drouin, J. (1987). Mol. Endocrinol. 1, 677–682.PubMedGoogle Scholar
  39. 39.
    Hall, S. H., Joseph, D. R., French, F. S., and Conti, M. (1988). Mol. Endocrinol. 2, 55–61.PubMedCrossRefGoogle Scholar
  40. 40.
    Hamil, K. G., Conti, M., Shimasaki, S., and Hall, S. H. (1994). Mol. Cell. Endocrinol. 99, 269–277.PubMedCrossRefGoogle Scholar
  41. 41.
    Morris, P. L., Vale, W. W., Cappel, S., and Bardin, C. W. (1988). Endocrinology 122, 717–725.PubMedCrossRefGoogle Scholar
  42. 42.
    Jenab, S. and Morris, P. L. (1998). Endocrinology 139, 1883–1890.PubMedCrossRefGoogle Scholar
  43. 43.
    Shan, L. X., Hardy, D. O., Catterall, J. F., and Hardy, M. P. (1995). Endocrinology 136, 1686–1693.PubMedCrossRefGoogle Scholar
  44. 44.
    Wong, H., Anderson, W. D., Cheng, T., and Riabowol, K. T. (1994). Anal. Biochem. 223, 251–258.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2000

Authors and Affiliations

  1. 1.Center for Biomedical ResearchPopulation Council and The Rockefeller UniversityNew York
  2. 2.The Rockefeller UniversityNew York

Personalised recommendations