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Degradation of LH-RH

  • Karl Bauer
  • Bernhard Horsthemke
Part of the Biochemical Endocrinology book series (BIOEND)

Abstract

The neuropeptide Luteinizing Hormone — Releasing Hormone (LH-RH, pyroGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) participates in synaptic events and the hypothalamic control of adenohypophyseal hormone secretion. Since the peptide is rapidly hydrolyzed by various tissue homogenates, it has been postulated that the biological inactivation of LH-RH at the target site is catalyzed by a peptidase, which might possibly be specific for this neuropeptide. Furthermore, it has been suggested that the feedback-controlled alterations of such an enzymatic activity might be involved in the regulation of the LH-RH metabolism and thus in the control of the biological activity of this peptide (Griffiths et al., 1975; Fridkin et al., 1977; Kuhl et al., 1978; Advis et al., 1982). Alternatively, it is conceivable that LH-RH is degraded by general proteolytic enzymes, which might fulfill a scavenger function at the site of target interaction (if located in the vicinity of the receptors) or a more general metabolic clearance function at other sites. It is clear that such enzymes cannot serve a regulatory function. For answering these questions it is a prerequisite to delineate the pathway of LH-RH fragmentation and to evaluate the biochemical properties of the enzymes capable of hydrolyzing this neuropeptide.

Keywords

Luteinizing Hormone General Proteolytic Enzyme Pyroglutamic Acid Estradiol Benzoate Prolyl Endopeptidase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Advis, J.P., Krause, J.E., and McKelvy, J.F., 1982, Luteinizing Hormone - Releasing Hormone peptidase activities in discrete hypothalamic regions and anterior pituitary of the rat: apparent regulation during the prepubertal period and first estrous cycle at puberty, Endocrinolgy 110: 1238CrossRefGoogle Scholar
  2. Bauer, K., and Kleinkauf, H., 1980, Catabolism of thyroliberin by rat adenohypophyseal tissue extract, Eur. J. Biochem. 106: 107PubMedCrossRefGoogle Scholar
  3. Bauer, K., Beier, S., Horsthemke, B., Knisatschek, H., and Sievers, J., 1980, Estrogen effects on LH-RH degrading brain and pituitary enzymes, Exptl. Brain Res. Suppl. 3: 93CrossRefGoogle Scholar
  4. Camargo, A.C.M.D., Fonseca, M.J.V.D., Caldo, H., and Carvalho, K.D.M., 1982, Influence of the carboxyl terminus of Luteinizing HormoneReleasing Hormone and bradykinin on hydrolysis by brainendooligopeptidases, J. Biol. Chem. 257: 9265PubMedGoogle Scholar
  5. Clayton, R.N., Shakespear, R.A., and Marshall, J.C., 1977, LH-RH degrading activity associated with a purified pituitary plasma membrane fraction, J. Endocrinol. 73: 34Google Scholar
  6. Elkabes, S., Fridkin, M., and Koch, Y., 1981, Studies on the enzymic degradation of Luteinizing Hormone - Releasing Hormone by rat pituitary plasma membranes, Biochem. Biophys. Res. Commun. 103: 240PubMedCrossRefGoogle Scholar
  7. Fridkin, M., Hazum, E., Baram, T., Lindner, H.R., and Koch, Y., 1977, Hypothalamic and pituitary LRF-degrading enzymes: characterization, purification and physiological role, in: Proceedings of the Vth American Peptide Symposium, Goodman, M., and Meienhofer, J., eds., Halsted Press, New York, p. 193Google Scholar
  8. Griffiths, E.C., Hooper, K.C., Jeffcoate, S.L., and Holland, D.T., 1975, The effects of gonadectomy and gonadal steroids on the activity of hypothalamic peptidases inactivating Luteinizing Hormone - Releasing Hormone (LH-RH), Brain Res. 88: 384PubMedCrossRefGoogle Scholar
  9. Hersh, L.B., and McKelvy, J.F., 1979, Enzymes involved in the degradation of Thyrotropin - Releasing Hormone (TRH) and Luteinizing Hormone - Releasing Hormone (LH-RH) in bovine brain, Brain Res. 168: 553PubMedCrossRefGoogle Scholar
  10. Horsthemke, B., and Bauer, K., 1980, Characterization of a nonchymotrypsinlike endopeptidase from anterior pituitary that hydrolyzes Luteinizing Hormone - Releasing Hormone at the tyrosylglycine and histidyl-tryptophane bonds, Biochemistry 19: 2867PubMedCrossRefGoogle Scholar
  11. Horsthemke, B., and Bauer, K., 1981, Chymotryptic-like hydrolysis of luliberin (LH-RF) by an adenohypophyseal enzyme of high molecular weight, Biochem. Biophys. Res. Commun. 103: 1322PubMedCrossRefGoogle Scholar
  12. Horsthemke, B., Knisatschek, H., Rivier, J., Sandow, J., and Bauer, K., 1981, Degradation of Luteinizing Hormone - Releasing Hormone and analogs by adenohypophyseal peptidases, Biochem. Biophys. Res. Commun. 100: 753PubMedCrossRefGoogle Scholar
  13. Horsthemke, B., and Bauer, K., 1982, Substrate specificity of an adenohypophyseal andopeptidase capable of hydrolyzing Luteinizing Hormone - Releasing Hormone: Preferential cleavage of peptide bonds involving the carboxyl terminus of hydrophobic and basic amino acids, Biochemistry 21: 1033PubMedCrossRefGoogle Scholar
  14. Horsthemke, B., Leblanc, P., Kordon, C., Wattiaux-De Coninck, S., Wattiaux, R., and Bauer, K., 1983, Subcellular distribution of particle-bound neutral peptidases capable of hydrolyzing gonadoliberin, thyroliberin, enkephalin and substance P, submittedGoogle Scholar
  15. Knisatschek, H., and Bauer, K., 1979, Characterization of “Thyroliberin deamidating enzyme” as a post-proline-cleaving enzyme, J. Biol. Chem. 254: 10936PubMedGoogle Scholar
  16. Knisatschek, H., Kleinkauf, H., and Bauer, K., 1980, Specific fluoro-genic substrates for the TRF-deamidating post-proline-cleaving enzyme, FEBS Lett. 111: 157PubMedCrossRefGoogle Scholar
  17. Koch, Y., Baram, T., Chobsieng, P., and Fridkin, M., 1974, Enzymic degradation of Luteinizing Hormone - Releasing Hormone (LH-RH) by hypothalamic tissue, Biochem. Biophys. Res. Commun. 61: 95PubMedCrossRefGoogle Scholar
  18. Koch, Y., Baram, T., Hazum, E., and Fridkin, M., 1977, Resistance to enzymic degradation of LH-RH analogues possessing increased biological activity, Biochem. Biophys. Res. Commun. 74: 488PubMedCrossRefGoogle Scholar
  19. Kuhl, H., Rosniatowski, C., and Taubert, H.D., 1978, The activity of an LH-RH-degrading enzyme in the anterior pituitary during the rat oestrus cycle and its alteration by injections of sex hormones, Acta endocr. (Kbh.) 87: 476Google Scholar
  20. Leblanc, P., Pattou, E., L’Heritier, A., and Kordon, C., 1980, Some properties of peptidasic activity bound to the anterior pituitary membranes, Biochem. Biophys. Res. Commun. 96: 1457PubMedCrossRefGoogle Scholar
  21. Leblanc, P., L’Heritier, A., Kordon, C., Horsthemke, B., Bauer, K., Wattiaux-De Coninck, S., Dubois, F., and Wattiaux, R., 1983, Characterization of a neutral metalloendopeptidase localized in the mitochondrial matrix of rat anterior pituitary tissue with GnRH as a substrate, submittedGoogle Scholar
  22. Loudes, C., Josepho-Bravo, P., Leblanc, P., and Kordon, C., 1978, Specific activity of LH-RH and TRH degrading enzymes in various tissues of normal and castrated male rats, Biochem. Biophys. Res. Commun. 83: 921PubMedCrossRefGoogle Scholar
  23. Nikolics, K., Szoke, B., Kéri, G., and Teplân, I., 1983, Gonadotropin-Releasing Hormone (GnRH) is not degraded by intact pituitary tissue in vitro, Biochem. Biophys. Res. Commun. 114: 1028PubMedCrossRefGoogle Scholar
  24. Orlowski, M., Wilk, E., Pearce, S., and Wilk, S., 1979, Purification and properties of a prolyl endopeptidase from rabbit brain, J. Neurochem. 33: 461PubMedCrossRefGoogle Scholar
  25. Szewczuk, A., and Mulczyk, M., 1969, Pyrrolidonyl peptidase in bacteria, Eur. J. Biochem. 8: 63PubMedCrossRefGoogle Scholar
  26. Wilk, S., and Orlowski, M., 1980, Cation-sensitive neutral endopeptidase: Isolation and specificity of the bovine pituitary enzyme, J. Neurochem. 35: 1172PubMedCrossRefGoogle Scholar
  27. Yoshimoto, T., Ogita, K., Walter, R., Koida, M., and Tsuru, D., 1979, Post-proline-cleaving enzyme, synthesis of a new fluorogenic substrate and distribution of the endopeptidase in rat tissues and body fluids of man, Biochim. Biophys. Acta 569: 184PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • Karl Bauer
    • 1
  • Bernhard Horsthemke
    • 1
  1. 1.Institut für BiochemieTechnische Universität BerlinBerlin (West)Germany

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