The Role of Carbohydrate Moiety of Gonadotropin Molecule in Transduction of Biological Signal

  • Uriel Zor
  • M. R. Sairam
  • Pnina Shentzer
  • Anat Azrad
  • Abraham Amsterdam
Part of the Biochemical Endocrinology book series (BIOEND)


Antagonists to small peptide hormones such as vasopressin, oxytocin, gonadotropin-releasing hormone (GnRH) and even to protein hormones such as adrenocorticotropin-hormone (ACTH) or glucagon have been known for many years. These antagonists were useful to establish the mode of action of these hormones. However, until recently, no clearly identified antagonists to glycoprotein hormones such as luteinizing hormone (LH), human chorionic gonadotropin (hCG), follicle stimulating hormone (FSH) and pregnant mare serum gonadotropin (PMSG) were available (for review see Sairam, 1983).


Luteinizing Hormone Granulosa Cell Adenylate Cyclase Follicle Stimulate Hormone Human Chorionic Gonadotropin 


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  1. Amsterdam, A., and Lindner, H.R., 1983, Localization of gonadotropin receptors in the gonads, in: “Electron Microscopy in Biology and Medicine: Current Topics in Ultrastructural Research”, P.M. Motta, ed., The Hague, The Netherlands, Martinus Nijhoff Publ., pp. 253–262.Google Scholar
  2. Amsterdam, A., Berkowitz, A., Nimrod, A. and Kohen, F., 1980, Aggregation of luteinizing hormone receptors in granulosa cells: A possible mechanism of desensitization to the hormone, Proc. Natl. Acad. Sci. U.S.A. 77:3440.Google Scholar
  3. Amsterdam, A., Naor, Z., Knecht, M., Dufau, M.L. and Catt, K.J., 1981, Hormone action and receptor redistribution in endocrine target cells: Gonadotropins and gonadotropin-releasing hormone, In: “Receptor-mediated Binding and Internalization of Toxins and Hormones”, J.L. Middlebrook and L.D. Kohn, eds., Academic Press, Inc., p. 283.Google Scholar
  4. Amsterdam, A., Nimrod, A., Lamprecht, S.A., Burstein, Y. and Lindner, H.R., 1979, Internalization and degradation of receptor-bound hCG in granulosa cell cultures, Am. J. Physiol. 236(2):E129.Google Scholar
  5. Amsterdam, A., Sairam, M.R., and Zor, U., 1983, Deglycosylated human chorionic gonadotropin retards the down-regulation of luteinizing hormone receptors in granulosa cells, J. Cell Biol., 97:407a.Google Scholar
  6. Channing, C.P., Sakai, C.N. and Bahl, 0.P., 1978, Role of the carbohydrate residues of human chorionic gonadotropin in binding and stimulation of adenosine 3’,8’-monophosphate accumulation by porcine granulosa cells, Endocrinology, 103: 341.PubMedCrossRefGoogle Scholar
  7. Chen, H-C., Shimohigashi, Y., Dufau, M.L., and Catt, K.J., 1982, Characterization and biological properties of chemically deglycosylated human chorionic gonadotropin. Role of carbohydrate moieties in adenylate cyclase activation, J. Biol. Chem. 257:14446.Google Scholar
  8. Combarnous, Y., Hennen, G., and Ketelslegers, J.M., 1978, Pregnant mare serum gonadotropin exhibits higher affinity for lutropin than for follitropin receptors of porcine testis, FEBS Lett. 90: 65.PubMedCrossRefGoogle Scholar
  9. Conn, P.M., Rogers, D.C., Stewart, J.M., Niedel, J. and Sheffield, T., 1982, Conversion of a gonadotropin-releasing hormone antagonist to an agonist, Nature, 296: 653.Google Scholar
  10. Dufau, M.L., Baukal, A.J. and Catt, K.J., 1980, Hormone-induced guanyl nucleotide binding and activation of adenylate cyclase in the Leydig cell, Proc. Natl. Acad. Sci. U.S.A. 77:5837.Google Scholar
  11. Giudicelli, Y., Lacasa, D. and Agli, B., 1979, Evidence for a second desensitized state of -adrenergic receptor with low affinity for ß-antagonists and normal reactivity towards 8-agonists in adipocyte membranes previously exposed to f3-antagonists, Eur. J. Biochem. 99:457.Google Scholar
  12. Goverman, J.M., Parsons, T.F. and Pierce, J.G., 1982, Enzymatic deglycosylation of the subunits of chorionic gonadotropin. Effects on formation of tertiary structure and biological activity, J. Biol. Chem. 257:15059.Google Scholar
  13. Hazum, E., 1981, Some characteristics of GnRH receptors in rat pituitary membranes: differences between an agonist and an antagonist, Mol. Cell. Endocr. 23:275.Google Scholar
  14. Kato, K., Sairam, M.R. and Manjunath, P., 1983, Inhibition of implantation and termination of pregnancy in the rat by a human chorionic gonadotropin antagonist, Endocrinology, 113: 195.Google Scholar
  15. Krupp, M. and Lane, M.D., 1981, On the mechanism of ligand-induced down-regulation of insulin receptor level in the liver cell, J. Biol. Chem. 256:1689.Google Scholar
  16. Lamprecht, S.A., Zor, U., Tsafriri, A. and Lindner, H.R., 1973, Action of prostaglandin Eland of luteinizing hormone on ovarian adenylate cyclase, protein kinase and ornithine decarboxylase activity during postnatal development and maturity in the rat, J. Endocr. 57:217.Google Scholar
  17. Lamprecht, S.A., Zor, U., Salomon, Y., Koch, Y., Ahrèn, K. and Lindner, H.R., 1977, Mechanism of hormonally induced refractoriness of ovarian adenylate cyclase to luteinizing hormone and prostaglandin E, J. Cyclic Nucl. Res. 3:69.Google Scholar
  18. Limbird, L.E., Gill, D.M. and Lefkowitz, R.J., 1980, Agonist-promoted coupling of the ß-adrenergic receptor with the guanine nucleotide regulatory protein of the adenylate cyclase system, Proc. Natl. Acad. Sci. U.S.A. 77:775.Google Scholar
  19. Manjunath, P. and Sairam, M.R., 1982, Biochemical, biological, and immunological properties of chemically deglycosylated human choriogonadotropin, J. Biol. Chem. 257:7109.Google Scholar
  20. Mock, E.J. and Niswender G.D., 1983, Differences in the rates of internalization of I-labeled human chorionic gonadotropin, luteinizing hormone, and epidermal growth factor by ovine lu-teal cells, Endocrinology, 113: 259.Google Scholar
  21. Mock, E.J., Papkoff, H. and Niswender, G.D., 1983, Internalization of ovine luteinizing hormone/human chorionic gonadotropin recombinants: Differential effects of the a-and E.-subunits, Endocrinology, 113: 265.Google Scholar
  22. Moyle, W.R., Bahl, 0.P. and Mgrz, L., 1975, Role of the carbohydrate of human chorionic gonadotropin in the mechanism of hormone action, J. Biol. Chem. 250: 9163.Google Scholar
  23. Mukherjee, C., Caron, M.G. and Lefkowitz, R.J., 1976, Regulation of adenylate cyclase coupled ß-adrenergic receptors by ß-adrenergic catecholamines, Endocrinology, 99: 347.Google Scholar
  24. Rebois, V.R., and Fishman, P.H., 1983, Deglycosylated human chorionic gonadotropin. An antagonist to desensitization and down-regulation of the gonadotropin receptor-adenylate cyclase system, J. Biol. Chem. 258:12775.Google Scholar
  25. Sairam, M.R., 1983, Gonadotropic hormones: Relationship between structure and function with emphasis on antagonists, Hormonal Proteins and Peptides, XI: 1.Google Scholar
  26. Sairam, M.R. and Manjunath, P., 1983, Hormonal antagpnistic properties of chemically deglycosylated human choriogonadotropin, J. Biol. Chem. 258: 445.Google Scholar
  27. Shechter, Y., Hernaez, L., Schlessinger, J. and Cuatrecasas. P. 1979, Local aggregation of hormone-receptor complexes is required,for activation by epidermal growth factor, Nature, 278: 835.Google Scholar
  28. Smith, M.A. and Vale, W.W., 1981, Desensitization to gonadotropinreleasing hormone observed in superfused pituitary cells on cytodex beads, Endocrinology, 108: 752.Google Scholar
  29. Stadel, J.M., Nambi, P., Lavin, T.N., Heald, S.L., Caron, G. and Lefkowitz, R.J., 1982, Catecholamine-induced desensitization of turkey erythrocyte adenylate cyclase. Structural alterations in the ß-adrenergic receptor revealed by photoaffinity labeling, J. Biol. Chem. 257:9242.Google Scholar
  30. Su, Y-F., Harden, K.T. and Perkins, J.P., 1979, Isoproterenol-induced desensitization of adenylate cyclase in human astrocytoma cells. Relation of loss of hormonal responsiveness and decrement in 8-adrenergic receptors, J. Biol. Chem. 254:38.Google Scholar
  31. Zor, U., Lamprecht, S.A., Kaneko, T., Schneider, H.P.G., McCann, S.M., Field, J.B., Tsafriri, A. and Lindner, H.R., 1972, Functional relations between cyclic AMP, prostaglandins and luteinizing hormone in rat pituitary and ovary, Adv. Cyclic. Nucl. Res. 1:503.Google Scholar
  32. Zor, U., Lamprecht, S.A., Misulovin, Z., Koch, Y. and Lindner, H.R., 1976, Refractoriness of ovarian adenylate cyclase to continued hormonal stimulation, Biochim. Biophys. Acta, 428:761.CrossRefGoogle Scholar
  33. Zor, U., Shentzer, P., Azrad, A., Sairam, M.R. and Amsterdam, A., 1984, Deglycosylated lutropin prevents desensitization of cyclic AMP response by lutropin: Dissociation between receptor uncoupling and down regulation, Endocrinology (in press).Google Scholar
  34. Zor, U., 1983, Role of cytoskeletal organization in the regulation of adenylate cyclase-cyclic adenosine monophosphate by hormones, Endocrine Rev. 4: 1.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • Uriel Zor
    • 1
  • M. R. Sairam
    • 2
  • Pnina Shentzer
    • 1
  • Anat Azrad
    • 1
  • Abraham Amsterdam
    • 1
  1. 1.Department of Hormone ResearchThe Weizmann Institute of ScienceRehovotIsrael
  2. 2.Reproduction Research LaboratoryClinical Research Institute of MontrealMontrealCanada

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