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The bioactivity of gonadotropin releasing hormones and its regulation in the gilthead seabream,Sparus aurata: in vivo andin vitro studies

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Abstract

Thein vivo andin vitro potency of native and modified forms of gonadotropin releasing hormone (GnRH) to release gonadotropin (GtH) was studied inSparus aurata and correlated with their relative susceptibility to degradation by cytosolic-bound enzymes of the pituitary, kidney, and liver. Salmon (s) GnRH and luteinizing hormone-releasing hormone (LHRH) are equipotent whereas analogs of these peptides ((D-Arg6-Pro9NET)-sGnRH, (D-Ala6-Pro9NET)-LHRH, (D-Trp6)-LHRH) are superactive in inducingin vivo GtH release (at 10 µg/kg body weight). In anin vitro superfusion system of pituitary fragments all analogs are equipotent to the native peptides (at 10−10 to 2.5 × 10−7M). sGnRH and LHRH are rapidly degraded by cytosolic peptidases of the pituitary, liver, and kidney. The preferred site of cleavage is the Tyr5-Gly6 bond. Substitution of the position 6 glycine by D-amino acids renders the 5–6 bond resistant to degradation and shifts the main site of cleavage to the Pro9-Gly10NH2 bond. Substitution at position 6 (as above) and at position 10 with Pro9NET results in analogs that are resistant to degradation. We propose that enzymatic cleavage terminates GnRH bioactivityin vivo and thus increased resistance to degradation is a major determinant of GnRH analog superactivity.

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References cited

  • Bauer, K. and Horsthemke, B. 1984. Degradation of LH-RH.In Hormonal Control of the Hypothalamo-Pituitary-Gonadal Axis. pp. 101–114. Edited by K.W. McKerns and Z. Naor. Plenum Press, New York.

    Google Scholar 

  • Crim, L.W. 1984. A variety of synthetic LHRH peptides stimulate gonadotropin hormone secretion in rainbow trout and the landlocked Atlantic salmon. J. Ster. Biochem. 20: 1390.

    Article  Google Scholar 

  • Crim, L.W., Wilson, C., St. Arnaud, R., Evans, D.M. and Harmin, S.A. 1987. Characteristics of fish pituitary LHRH receptors.In Proc. Third Int. Symp. on Reprod. Physiol. Fish. pp. 21–23. Edited by D.R. Idler, L.W. Crim and J. Walsh. Memorial University Press, St. John's.

    Google Scholar 

  • De Leeuw, R., Smit-Van Dijk, W., Van't Veer, C., Beumer, P., Goos, H.J.Th. and Van Oordt, P.G.W.J. 1987. Gonadotropin-releasing hormone agonists: Their relative binding affinity and biological activity in the African catfish,Clarias gariepnus.In Proc. Third Int. Symp. on Reprod. Physiol. Fish. p. 27. Edited by D.R. Idler, L.W. Crim and J. Walsh. Memorial University Press. St. John's.

    Google Scholar 

  • Donaldson, E.M., Van Der Kraak, G., Hunter, G.A., Dye, H.M., Rivier, H. and Vale, W. 1984. Teleost GnRH and analogs: Effect on plasma GtH concentration and ovulation in coho salmon (Oncorhynchus kisutch). Gen. Comp. Endocrinol. 53: 458–459.

    Google Scholar 

  • Habibi, H.R., Peter, R.E., Sokolowska, M., Rivier, J.E. and Vale, W.W. 1987a. Characterization of gonadotropin-releasing hormone (GnRH) binding to pituitary receptors in goldfish (Carassius auratus). Biol. Reprod. 36: 844–853.

    Article  PubMed  CAS  Google Scholar 

  • Habibi, H.R., Van Der Loo, H., Marchant, T.A. and Peter, R.E. 1987b. Relationship between GnRH receptor binding and biological activity in the goldfish pituitary.In Proc. Third Int. Symp. on Reprod. Physiol. Fish. p. 28. Edited by D.R. Idler, L.W. Crim and J.M. Walsh. Memorial University Press, St. John's.

    Google Scholar 

  • Horsthemke, B. and Bauer, K. 1980. Characterization of a non-chymotrypsin-like endopeptidase from anterior pituitary that hydrolyzes luteinizing hormone releasing hormone at the tyrosyl-glycine and histidyl-tryptophan bonds. Biochemistry 19: 2867–2873.

    Article  PubMed  CAS  Google Scholar 

  • Horsthemke, B., Knisatchek, H., Rivier, J., Sandow, J. and Bauer, K. 1981. Degradation of luteinizing hormone-releasing hormone and analogs by adenohypophyseal peptidases. Biochem. Biophys. Res. Comm. 100: 753–759.

    Article  PubMed  CAS  Google Scholar 

  • Horvath, A., Keri, G., Gulyas, T., Vigh, S., Nikolics, K. and Telpan, I. 1986. Comparison ofin vitro andin vivo effects of different species specific GnRH and their analogs. Biochem. Biophys. Res. Comm. 138: 419–426.

    Article  PubMed  CAS  Google Scholar 

  • Huang, Y.P. and Peter, R.E. 1988. Evidence for a gonadotropin-releasing hormone binding protein in goldfish (Carassius auratus) serum. Gen. Comp. Endocrinol. 69: 308–316.

    Article  PubMed  CAS  Google Scholar 

  • Koch, Y., Elkabes, S. and Fridkin, M. 1984. Degradation of luteinizing hormone-releasing hormone by rat pituitary plasma membrane associated enzymes.In Hormonal Control of the Hypothalamo-Pituitary-Gonadal Axis. pp. 115–126. Edited by K.W. McKerns and Z. Naor. Plenum Press, New York.

    Google Scholar 

  • Krause, J.E., Advis, J.P. and McKelvy, J.F. 1982. Characterization of the site of cleavage of luteinizing hormone-releasing hormone under conditions of measurement in which LHRH degradation undergoes physiologically related change. Biochem. Biophys. Res. Comm. 108: 1475–1481.

    Article  PubMed  CAS  Google Scholar 

  • Levavi-Zermonsky, B. and Yaron, Z. 1987. Gonadotropin secretion from the pituitary of tilapia: stimulation of GnRH and possible mode of action.In Proc. Third Int. Symp. of Reprod. Physiol. Fish. p. 32. Edited by D.R. Idler, L.W. Crim and J.M. Walsh. Memorial University Press, St. John's.

    Google Scholar 

  • Lin, H.R., Van Der Kraak, G., Zhou, X.J., Liang, J.Y., Peter, R.E., Rivier, J.E. and Vale, W.W. 1988. Effects of (D-Arg6, Trp7, Leu8, Pro9NET) hormone-releasing hormone (sGnRHA) and (D-Ala6, Pro9NET)-luteinizing hormone-releasing hormone (LHRH-A), in combination with pimozide or domperidone, on gonadotropin release and ovulation in the Chinese loach and common carp. Gen. Comp. Endocrinol. 69: 31–40.

    Article  PubMed  CAS  Google Scholar 

  • MacKenzie, D.S., Gould, D.R., Peter, R.E., Rivier, J. and Vale, W.W. 1984. Response of superfused goldfish pituitary fragments to mammalian and salmon gonadotropin-releasing hormones. Life Sci. 35: 2019–2026.

    Article  PubMed  CAS  Google Scholar 

  • McKelvy, J.F. and Blumberg, S. 1986. Inactivation and metabolism of neuropeptides. Ann. Rev. Neurosci. 9: 415–434.

    Article  PubMed  CAS  Google Scholar 

  • Peter, R.E., Lin, H.R. and Van Der Kraak, G. 1987a. Drug/hormone induced breeding of Chinese teleosts.In Proc. Third Int. Symp. on Reproductive Physiology of Fish. pp. 120–123. Edited by D.R. Idler, L.W. Crim and J.M. Walsh. Memorial University Press, St. John's.

    Google Scholar 

  • Peter, R.E. Nahorniak, C.S., Shih, S., King, J.A. and Millar, R.P. 1987b. Activity of position-8-substituted analogs of mammalian gonadotropin-releasing hormone (mGnRH) and chicken and lamprey gonadotropin-releasing hormones in goldfish. Gen. Comp. Endocrinol. 65: 385–393.

    Article  PubMed  CAS  Google Scholar 

  • Peter, R.E., Chang, J.P., Nahorniak, C.S., Omeljaniuk, R.J., Sokolowska, M., Shih, S.H. and Billard, R. 1986. Interactions of catecholamines and GnRH in regulation of gonadotropin secretion in teleost fish. Rec. Prog. Horm. Res. 42: 513–548.

    PubMed  CAS  Google Scholar 

  • Peter, R.E., Nahorniak, C.S., Sokolowska, M., Chang, J.P., Rivier, J.E., Vale, W.W., King, J.A. and Millar, R.P. 1985. Structure-activity relationships of mammalian, chicken, and salmon gonadotropin releasing hormonesin vivo in goldfish. Gen. Comp. Endocrinol. 58: 231–242.

    Article  PubMed  CAS  Google Scholar 

  • Sherwood, N.M. 1987. Brain peptides in the control of fish reproduction.In Proc. Third Int. Symp. on Reprod. Physiol. Fish. pp. 5–15. Edited by D.R. Idler, L.W. Crim and J.M. Walsh. Memorial University Press, St. John's.

    Google Scholar 

  • Sherwood, N., Eiden, L., Brownstein, M., Spiess, J., Rivier, J. and Vale, W. 1983. Characterization of a teleost Gn-RH. Proc. Nat. Acad. Sci. U.S.A. 80: 2794–2798.

    Article  CAS  Google Scholar 

  • Siegel, S. 1956. Nonparametric statistics for the behavioral sciences. McGraw-Hill, New York.

    Google Scholar 

  • Sower, S.A., King, J.A., Millar, R.P., Sherwood, N.M. and Marshak, D.R. 1987. Comparative biological properties of lamprey gonadotropin-releasing hormones in vertebrates. Endocrinology 120: 773–779.

    Article  PubMed  CAS  Google Scholar 

  • Van Der Kraak, G., Lin, H.R., Donaldson, E.M., Dye, H.M. and Hunter, G.A. 1983. Effects of LH-RH and des-Gly10 (D-Ala6)-LH-RH-ethylamide on plasma gonadotropin levels and oocyte maturation in adult female coho salmon (Oncorhynchus kisutch). Gen. Comp. Endocrinol. 49: 470–476.

    Article  PubMed  Google Scholar 

  • Weil, C., Hansen, P., Hyam, D., Le Gac, F., Breton, B. and Crim, L.W. 1986. Use of pituitary cells in primary culture to study the regulation of gonadotropin hormone (GtH) secretion in rainbow trout: setting up and validating the system as assessed by its responsiveness to mammalian and salmon gonadotropin releasing hormone. Gen. Comp. Endocrinol. 62: 202–209.

    Article  PubMed  CAS  Google Scholar 

  • Zohar, Y. 1988. Gonadotropin-releasing hormone in spawning induction in teleosts: Basic and applied considerations.In Reproduction in Fish: Basic and Applied Aspects in Endocrinology and Genetics. pp. 47–62. Edited by Y. Zohar and B. Breton. INRA Press, Paris.

    Google Scholar 

  • Zohar, Y. and Gordin, H. 1979. Spawning kinetics in the gilt-head sea-bream,Sparus aurata (L.) after low doses of human chorionic gonadotropin. J. Fish Biol. 15: 665–670.

    Article  CAS  Google Scholar 

  • Zohar, Y., Pagelson, G., Tosky, M. and Finkelman, Y. 1987. GnRH control of gonadotropin secretion, ovulation and spawning in the gilthead seabreamSparus aurata. 1987.In Proc. Third Int. Symp. on Reprod. Physiol. Fish. p. 106. Edited by D.R. Idler, L.W. Crim and J.M. Walsh. Memorial University Press, St. John's.

    Google Scholar 

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Authors and Affiliations

  1. National Center for Mariculture, Israel Oceanographic and Limnological Research, Eilat

    Y. Zohar, A. Goren, M. Tosky, G. Pagelson & D. Leibovitz

  2. Department of Hormone Research, Weizmann Institute of Science, Rehovot, Israel

    Y. Koch

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  1. Y. Zohar
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  2. A. Goren
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  3. M. Tosky
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  4. G. Pagelson
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  5. D. Leibovitz
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  6. Y. Koch
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Zohar, Y., Goren, A., Tosky, M. et al. The bioactivity of gonadotropin releasing hormones and its regulation in the gilthead seabream,Sparus aurata: in vivo andin vitro studies. Fish Physiol Biochem 7, 59–67 (1989). https://doi.org/10.1007/BF00004690

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