Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Oct 1;88(19):8801–8805. doi: 10.1073/pnas.88.19.8801

Production of leukotrienes in gonadotropin-releasing hormone-stimulated pituitary cells: potential role in luteinizing hormone release.

L Kiesel 1, A F Przylipiak 1, A J Habenicht 1, M S Przylipiak 1, B Runnebaum 1
PMCID: PMC52598  PMID: 1656455

Abstract

Gonadotropin-releasing hormone (GnRH) stimulated the formation of two major metabolites of the 5-lipoxygenase pathway, leukotriene (LT) B4 and LTC4, as well as luteinizing hormone (LH) release in primary cultures of rat anterior pituitary cells. Several lines of evidence suggested the presence of a GnRH-dependent pituitary endocrine system in which LTs act as second messengers for LH release: (i) GnRH-dependent LT formation was observed within 1 min and immediately preceded GnRH-induced LH release, whereas exogenous LTs stimulated LH release at low concentrations; (ii) the dose responses of GnRH-induced LT production and LH release were similar and both effects required the presence of extracellular Ca2+ ions; (iii) GnRH-induced LH release was blocked by up to 45% following the administration of several LT receptor antagonists; (iv) LTE4 action on LH secretion was entirely abolished by LT receptor antagonists; and (v) an activator of protein kinase C acted synergistically with LTE4 to induce LH release. The major source of LT formation in the pituitary cell cultures appeared to be the gonadotrophs, as shown by GnRH receptor desensitization experiments. The results demonstrate the presence of a GnRH-activatable 5-lipoxygenase pathway in anterior pituitary cells and provide strong support for the hypothesis that LTs play a role in LH release in the GnRH signaling pathway.

Full text

PDF
8801

Selected References

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

  1. Andrews W. V., Conn P. M. Gonadotropin-releasing hormone stimulates mass changes in phosphoinositides and diacylglycerol accumulation in purified gonadotrope cell cultures. Endocrinology. 1986 Mar;118(3):1148–1158. doi: 10.1210/endo-118-3-1148. [DOI] [PubMed] [Google Scholar]
  2. Borgeat P., Samuelsson B. Arachidonic acid metabolism in polymorphonuclear leukocytes: effects of ionophore A23187. Proc Natl Acad Sci U S A. 1979 May;76(5):2148–2152. doi: 10.1073/pnas.76.5.2148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chang J. P., Graeter J., Catt K. J. Dynamic actions of arachidonic acid and protein kinase C in pituitary stimulation by gonadotropin-releasing hormone. Endocrinology. 1987 May;120(5):1837–1845. doi: 10.1210/endo-120-5-1837. [DOI] [PubMed] [Google Scholar]
  4. Conn P. M., Huckle W. R., Andrews W. V., McArdle C. A. The molecular mechanism of action of gonadotropin releasing hormone (GnRH) in the pituitary. Recent Prog Horm Res. 1987;43:29–68. doi: 10.1016/b978-0-12-571143-2.50007-1. [DOI] [PubMed] [Google Scholar]
  5. Goerig M., Habenicht A. J., Zeh W., Salbach P., Kommerell B., Rothe D. E., Nastainczyk W., Glomset J. A. Evidence for coordinate, selective regulation of eicosanoid synthesis in platelet-derived growth factor-stimulated 3T3 fibroblasts and in HL-60 cells induced to differentiate into macrophages or neutrophils. J Biol Chem. 1988 Dec 25;263(36):19384–19391. [PubMed] [Google Scholar]
  6. Gorospe W. C., Conn P. M. Agents that decrease gonadotropin-releasing hormone (GnRH) receptor internalization do not inhibit GnRH-mediated gonadotrope desensitization. Endocrinology. 1987 Jan;120(1):222–229. doi: 10.1210/endo-120-1-222. [DOI] [PubMed] [Google Scholar]
  7. Habenicht A. J., Goerig M., Rothe D. E., Specht E., Ziegler R., Glomset J. A., Graf T. Early reversible induction of leukotriene synthesis in chicken myelomonocytic cells transformed by a temperature-sensitive mutant of avian leukemia virus E26. Proc Natl Acad Sci U S A. 1989 Feb;86(3):921–924. doi: 10.1073/pnas.86.3.921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hirota K., Hirota T., Aguilera G., Catt K. J. Hormone-induced redistribution of calcium-activated phospholipid-dependent protein kinase in pituitary gonadotrophs. J Biol Chem. 1985 Mar 25;260(6):3243–3246. [PubMed] [Google Scholar]
  9. Hulting A. L., Lindgren J. A., Hökfelt T., Eneroth P., Werner S., Patrono C., Samuelsson B. Leukotriene C4 as a mediator of luteinizing hormone release from rat anterior pituitary cells. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3834–3838. doi: 10.1073/pnas.82.11.3834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hulting A. L., Lingren J. A., Hökfelt T., Heidvall K., Eneroth P., Werner S., Patrono C., Samuelsson B. Leukotriene C4 stimulates LH secretion from rat pituitary cells in vitro. Eur J Pharmacol. 1984 Nov 13;106(2):459–460. doi: 10.1016/0014-2999(84)90742-8. [DOI] [PubMed] [Google Scholar]
  11. Kiesel L., Bertges K., Rabe T., Runnebaum B. Gonadotropin releasing hormone enhances polyphosphoinositide hydrolysis in rat pituitary cells. Biochem Biophys Res Commun. 1986 Jan 29;134(2):861–867. doi: 10.1016/s0006-291x(86)80499-5. [DOI] [PubMed] [Google Scholar]
  12. Kiesel L., Lukács G. L., Eberhardt I., Runnebaum B., Spät A. Effect of inositol 1,4,5-trisphosphate and GTP on calcium release from pituitary microsomes. FEBS Lett. 1987 Jun 8;217(1):85–88. doi: 10.1016/0014-5793(87)81248-6. [DOI] [PubMed] [Google Scholar]
  13. Kiesel L., Przylipiak A., Rabe T., Runnebaum B. Leukotrienes stimulate gonadotropin release in vitro. Gynecol Endocrinol. 1987 Mar;1(1):25–35. doi: 10.3109/09513598709082693. [DOI] [PubMed] [Google Scholar]
  14. Kiesel L., Przylipiak A., Rabe T., Runnebaum B. The role of novel arachidonic acid metabolites in GnRH action on gonadotrophin release in vitro. Hum Reprod. 1986 Sep;1(6):349–352. doi: 10.1093/oxfordjournals.humrep.a136421. [DOI] [PubMed] [Google Scholar]
  15. Kiesel L., Rabe T., Hauser G., Przylipiak A., Jadali F., Runnebaum B. Stimulation of luteinizing hormone release by melittin and phospholipase A2 in rat pituitary cells. Mol Cell Endocrinol. 1987 May;51(1-2):1–6. doi: 10.1016/0303-7207(87)90111-0. [DOI] [PubMed] [Google Scholar]
  16. Lindgren J. A., Hulting A. L., Hökfelt T., Dahlén S. E., Eneroth P., Werner S., Patrono C., Samuelsson B. Evidence for leukotriene formation and a neuroendocrine role for leukotriene C4 in rat brain. Adv Prostaglandin Thromboxane Leukot Res. 1985;15:561–564. [PubMed] [Google Scholar]
  17. Lindgren J. A., Hökfelt T., Dahlén S. E., Patrono C., Samuelsson B. Leukotrienes in the rat central nervous system. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6212–6216. doi: 10.1073/pnas.81.19.6212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Loumaye E., Catt K. J. Homologous regulation of gonadotropin-releasing hormone receptors in cultured pituitary cells. Science. 1982 Feb 19;215(4535):983–985. doi: 10.1126/science.6296998. [DOI] [PubMed] [Google Scholar]
  19. Mathews W. R., Rokach J., Murphy R. C. Analysis of leukotrienes by high-pressure liquid chromatography. Anal Biochem. 1981 Nov 15;118(1):96–101. doi: 10.1016/0003-2697(81)90162-7. [DOI] [PubMed] [Google Scholar]
  20. Naor Z., Kiesel L., Vanderhoek J. Y., Catt K. J. Mechanism of action of gonadotropin releasing hormone: role of lipoxygenase products of arachidonic acid in luteinizing hormone release. J Steroid Biochem. 1985 Nov;23(5B):711–717. doi: 10.1016/s0022-4731(85)80006-6. [DOI] [PubMed] [Google Scholar]
  21. Powell W. S. Rapid extraction of arachidonic acid metabolites from biological samples using octadecylsilyl silica. Methods Enzymol. 1982;86:467–477. doi: 10.1016/0076-6879(82)86218-6. [DOI] [PubMed] [Google Scholar]
  22. Przylipiak A., Kiesel L., Habenicht A. J., Przylipiak M., Runnebaum B. Exogenous action of 5-lipoxygenase by its metabolites on luteinizing hormone release in rat pituitary cells. Mol Cell Endocrinol. 1990 Feb 12;69(1):33–39. doi: 10.1016/0303-7207(90)90086-n. [DOI] [PubMed] [Google Scholar]
  23. Samuelsson B., Dahlén S. E., Lindgren J. A., Rouzer C. A., Serhan C. N. Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science. 1987 Sep 4;237(4819):1171–1176. doi: 10.1126/science.2820055. [DOI] [PubMed] [Google Scholar]
  24. Snyder G. D., Capdevila J., Chacos N., Manna S., Falck J. R. Action of luteinizing hormone-releasing hormone: involvement of novel arachidonic acid metabolites. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3504–3507. doi: 10.1073/pnas.80.11.3504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Vanderhoek J. Y., Kiesel L., Naor Z., Bailey J. M., Catt K. J. Arachidonic acid metabolism in gonadotroph-enriched pituitary cells. Prostaglandins Leukot Med. 1984 Sep;15(3):375–385. doi: 10.1016/0262-1746(84)90136-7. [DOI] [PubMed] [Google Scholar]
  26. Vegesna R. V., Mong S., Crooke S. T. Leukotriene D4-induced activation of protein kinase C in rat basophilic leukemia cells. Eur J Pharmacol. 1988 Mar 15;147(3):387–396. doi: 10.1016/0014-2999(88)90173-2. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES