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. 1986 Aug;83(16):5963–5967. doi: 10.1073/pnas.83.16.5963

Interpretation of dose-response curves for luteinizing hormone release by gonadotropin-releasing hormone, related peptides, and leukotriene C4 according to a hormone/receptor/effector model.

J Leiser, P M Conn, J J Blum
PMCID: PMC386417  PMID: 3016732

Abstract

The dose-response curves for pituitary luteinizing hormone (LH) release in response to gonadotropin-releasing hormone and its agonists are unusually broad. It appears, however, that these ligands bind to a single class of receptors. It is shown that these dose-response data can be explained by either of two models in which ligand-receptor complexes stimulate LH secretion by interacting with either of two different effector systems or by interacting with a single effector system but forming monomeric and dimeric active effector complexes. A combination of these two basic models can account for the very broad, biphasic dose-response curve reported for LH release in response to leukotriene C4.

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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. Blum J. J., Conn P. M. Gonadotropin-releasing hormone stimulation of luteinizing hormone release: A ligand-receptor-effector model. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7307–7311. doi: 10.1073/pnas.79.23.7307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Clayton R. N., Catt K. J. Gonadotropin-releasing hormone receptors: characterization, physiological regulation, and relationship to reproductive function. Endocr Rev. 1981 Spring;2(2):186–209. doi: 10.1210/edrv-2-2-186. [DOI] [PubMed] [Google Scholar]
  4. Clayton R. N., Shakespear R. A., Duncan J. A., Marshall J. C. Luteinizing hormone-releasing hormone inactivation by purified pituitary plasma membranes: effects of receptor-binding studies. Endocrinology. 1979 May;104(5):1484–1494. doi: 10.1210/endo-104-5-1484. [DOI] [PubMed] [Google Scholar]
  5. Clayton R. N., Shakespear R. A., Duncan J. A., Marshall J. C., Munson P. J., Rodbard D. Radioiodinated nondegradable gonadotropin-releasing hormone analogs: new probes for the investigation of pituitary gonadotropin-releasing hormone receptors. Endocrinology. 1979 Dec;105(6):1369–1376. doi: 10.1210/endo-105-6-1369. [DOI] [PubMed] [Google Scholar]
  6. Conn P. M., Ganong B. R., Ebeling J., Staley D., Neidel J. E., Bell R. M. Diacylglycerols release LH: structure-activity relations reveal a role for protein kinase C. Biochem Biophys Res Commun. 1985 Jan 16;126(1):532–539. doi: 10.1016/0006-291x(85)90638-2. [DOI] [PubMed] [Google Scholar]
  7. Conn P. M., Rogers D. C., Sandhu F. S. Alteration of the intracellular calcium level stimulates gonadotropin release from cultured rat anterior pituitary cells. Endocrinology. 1979 Nov;105(5):1122–1127. doi: 10.1210/endo-105-5-1122. [DOI] [PubMed] [Google Scholar]
  8. Conn P. M., Rogers D. C., Stewart J. M., Niedel J., Sheffield T. Conversion of a gonadotropin-releasing hormone antagonist to an agonist. Nature. 1982 Apr 15;296(5858):653–655. doi: 10.1038/296653a0. [DOI] [PubMed] [Google Scholar]
  9. Conn P. M., Staley D., Harris C., Andrews W. V., Gorospe W. C., McArdle C. A., Huckle W. R., Hansen J. Mechanism of action of gonadotropin releasing hormone. Annu Rev Physiol. 1986;48:495–513. doi: 10.1146/annurev.ph.48.030186.002431. [DOI] [PubMed] [Google Scholar]
  10. Corvera S., Huerta-Bahena J., Pelton J. T., Hruby V. J., Trivedi D., García-Sáinz J. A. Metabolic effects and cyclic AMP levels produced by glucagon, (1-N alpha-Trinitrophenylhistidine,12-homoarginine)glucagon and forskolin in isolated rat hepatocytes. Biochim Biophys Acta. 1984 Aug 17;804(4):434–441. doi: 10.1016/0167-4889(84)90071-5. [DOI] [PubMed] [Google Scholar]
  11. De Lean A., Stadel J. M., Lefkowitz R. J. A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupled beta-adrenergic receptor. J Biol Chem. 1980 Aug 10;255(15):7108–7117. [PubMed] [Google Scholar]
  12. García-Sáinz J. A., Hernández-Sotomayor S. M. Adrenergic regulation of gluconeogenesis: possible involvement of two mechanisms of signal transduction in alpha 1-adrenergic action. Proc Natl Acad Sci U S A. 1985 Oct;82(20):6727–6730. doi: 10.1073/pnas.82.20.6727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Garrity M. J., Andreasen T. J., Storm D. R., Robertson R. P. Prostaglandin E-induced heterologous desensitization of hepatic adenylate cyclase. Consequences on the guanyl nucleotide regulatory complex. J Biol Chem. 1983 Jul 25;258(14):8692–8697. [PubMed] [Google Scholar]
  14. Harris C. E., Staley D., Conn P. M. Diacylglycerols and protein kinase C. Potential amplifying mechanism for Ca2+-mediated gonadotropin-releasing hormone-stimulated luteinizing hormone release. Mol Pharmacol. 1985 May;27(5):532–536. [PubMed] [Google Scholar]
  15. Hsia J. A., Hewlett E. L., Moss J. Heterologous desensitization of adenylate cyclase with prostaglandin E1 alters sensitivity to inhibitory as well as stimulatory agonists. J Biol Chem. 1985 Apr 25;260(8):4922–4926. [PubMed] [Google Scholar]
  16. 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]
  17. Jacobs S., Cuatrecasas P. The mobile receptor hypothesis and "cooperativity" of hormone binding. Application to insulin. Biochim Biophys Acta. 1976 May 21;433(3):482–495. doi: 10.1016/0005-2736(76)90275-3. [DOI] [PubMed] [Google Scholar]
  18. Kassis S., Fishman P. H. Different mechanisms of desensitization of adenylate cyclase by isoproterenol and prostaglandin E1 in human fibroblasts. Role of regulatory components in desensitization. J Biol Chem. 1982 May 10;257(9):5312–5318. [PubMed] [Google Scholar]
  19. Koch B. D., Dorflinger L. J., Schonbrunn A. Pertussis toxin blocks both cyclic AMP-mediated and cyclic AMP-independent actions of somatostatin. Evidence for coupling of Ni to decreases in intracellular free calcium. J Biol Chem. 1985 Oct 25;260(24):13138–13145. [PubMed] [Google Scholar]
  20. Kéri G., Nikolics K., Teplán I., Molnár J. Desensitization of luteinizing hormone release in cultured pituitary cells by gonadotropin-releasing hormone. Mol Cell Endocrinol. 1983 Apr;30(1):109–120. doi: 10.1016/0303-7207(83)90205-8. [DOI] [PubMed] [Google Scholar]
  21. Marian J., Conn P. M. Gonadotropin releasing hormone stimulation of cultured pituitary cells requires calcium. Mol Pharmacol. 1979 Jul;16(1):196–201. [PubMed] [Google Scholar]
  22. Marian J., Cooper R. L., Conn P. M. Regulation of the rat pituitary gonadotropin-releasing hormone receptor. Mol Pharmacol. 1981 May;19(3):399–405. [PubMed] [Google Scholar]
  23. Minton A. P. Steady-state relations between hormone binding and elicited response: quantitative mechanistic models. Horiz Biochem Biophys. 1982;6:43–65. [PubMed] [Google Scholar]
  24. Naor Z., Clayton R. N., Catt K. J. Characterization of gonadotropin-releasing hormone receptors in cultured rat pituitary cells. Endocrinology. 1980 Oct;107(4):1144–1152. doi: 10.1210/endo-107-4-1144. [DOI] [PubMed] [Google Scholar]
  25. Palfrey H. C., Alper S. L., Greengard P. Protein phosphorylation and the regulation of cation cotransport. J Exp Biol. 1980 Dec;89:103–115. doi: 10.1242/jeb.89.1.103. [DOI] [PubMed] [Google Scholar]
  26. Reynolds J. A. Interaction of divalent antibody with cell surface antigens. Biochemistry. 1979 Jan 23;18(2):264–269. doi: 10.1021/bi00569a004. [DOI] [PubMed] [Google Scholar]
  27. Smith M. A., Perrin M. H., Vale W. W. Desensitization of cultured pituitary cells to gonadotropin-releasing hormone: evidence for a post-receptor mechanism. Mol Cell Endocrinol. 1983 Apr;30(1):85–96. doi: 10.1016/0303-7207(83)90203-4. [DOI] [PubMed] [Google Scholar]

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