Journal of Endocrinological Investigation

, Volume 26, Issue 3, pp 211–215 | Cite as

Effect of a synthetic pineal tetrapeptide (Ala-Glu-Asp-Gly) on melatonin secretion by the pineal gland of young and old rats

  • Y. Djeridane
  • V. Kh. Khavinson
  • V. N. Anisimov
  • Yvan Touitou
Original Article


The pineal gland contains many peptides known to be implicated in melatonin production. We examined the effects of a synthetic pineal tetrapeptide Ala-Glu-Asp-Gly on melatonin secretion by the pineal gland. The tetrapeptide effects on pineal gland melatonin secretion were studied in young (9 weeks) and old (27 months) male Wistar rats using a perifusion device. Pineal tetrapeptide at the concentrations used (10–4 to 10–6 M) had no significant effect upon melatonin secretion whatever the age of the animals, young or old. We also looked at the effect of the tetrapeptide on pineal melatonin stimulated by a β-adrenergic agonist, isoproterenol. We found that isoproterenol-induced melatonin increase was not modified by the tetrapeptide. Our results suggest that the pineal tetrapeptide Ala-Glu-Asp-Gly, does not seem to play a role, at least in vitro, in the control of melatonin secretion by the rat pineal gland.


Pineal tetrapeptide melatonin pineal gland aging rat 


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  1. 1.
    Reiter R.J. Pineal melatonin: Cell biology of its synthesis and of its physiological interactions. Endocr. Rev. 1991, 12: 151–180.PubMedCrossRefGoogle Scholar
  2. 2.
    Touitou Y., Fevre M., Bogdan A. et al. Patterns of plasma melatonin with ageing and mental condition: stability of nyctohemeral rhythms and differences in seasonal variation. Acta Endocrinol. 1984, 106: 145–151.PubMedGoogle Scholar
  3. 3.
    Waldhauser F., Kovacs J., Reiter E. Age-related changes in melatonin levels in humans and its potential consequences for sleep disorders. Exp. Gerontol. 1998, 33: 759–772.PubMedCrossRefGoogle Scholar
  4. 4.
    Touitou Y., Haus E. Alterations with aging of the endocrine and neuroendocrine circadian system in humans. Chronobiol. Int. 2000, 17: 369–390.PubMedCrossRefGoogle Scholar
  5. 5.
    Touitou Y. Human aging and melatonin. Clinical relevance. Exp. Gerontol. 2001, 36: 1083–1100.PubMedCrossRefGoogle Scholar
  6. 6.
    Reiter R.J., Tan D.X., Cabrera J. et al. The oxidant/antioxidant network: role of melatonin. Biol. Signals Recept. 1999, 8: 56–63.PubMedCrossRefGoogle Scholar
  7. 7.
    Gitto E., Tan D.X., Reiter R.J. et al. Individual and synergistic antioxidative actions of melatonin: studies with vitamin E, vitamin C, glutathione and desferrioxamine (desferoxamine) in rat liver homogenates. J. Pharm. Pharmacol. 2001, 53: 1393–1401.PubMedCrossRefGoogle Scholar
  8. 8.
    Buijs R.M., Pévet P. Vasopressin- and oxytocin-containing fibres in the pineal gland and subcomissural organ of the rat. Cell Tissue Res. 1980, 205: 11–17.PubMedCrossRefGoogle Scholar
  9. 9.
    Simonneaux V., Ribeleyga C., Miguez J.M., Pévet P. Physiological role of neuropeptides in the mammalian pineal gland. In: Tang P.L., Pang S.F., Reiter R.J. (Eds.), Melatonin: A universal photoperiodic signal with diverse actions. Front. Horm. Res. Karger, Basel, 1996, p. 24.Google Scholar
  10. 10.
    Simonneaux V., Vuillez P., Eder U., Miguez J.M., Pévet P., Fischer-Colbrie R. Secretoneurin: a new neuropeptide in the rodent pineal gland. Cell Tissue Res. 1997, 288: 427–434.PubMedCrossRefGoogle Scholar
  11. 11.
    Yuwiler A., Brammer G.L. Neurotransmitters and peptides in the pineal gland. In: Wetterberg L. (Ed.), light and biological rhythms in man. Pergamon Press, Oxford, 1993, p. 133.Google Scholar
  12. 12.
    Yuwiler A., Brammer, G.L., Bennett B.L. Interaction between adrenergic and peptide stimulation in the rat pineal: pituitary adenylate cyclase-activating peptide. J. Neurochem. 1995, 64: 2273–2280.PubMedCrossRefGoogle Scholar
  13. 13.
    Mikkelsen J.D., Hauser F., deLecea L. et al. Hypocretin (orexin) in the rat pineal gland: a central transmitter with effects on noradrenaline-induced release of melatonin. Eur. J. Neurosci. 2001, 14: 419–425.PubMedCrossRefGoogle Scholar
  14. 14.
    Anisimov V.N., Bondarenko L.A., Khavinson V.Kh. The pineal peptides: Interaction with indoles and the role in aging and cancer. In: Gupta D., Wollmann H.A., Ranke M.B. (Eds.), Neuroendocrinology: New frontiers. Brain Research Promotion, London, 1990, p. 317.Google Scholar
  15. 15.
    Anisimov V.N., Bondarenko L.A., Khavinson V.Kh. Effect of pineal peptide preparation (Epithalamin) on life span and pineal and serum melatonin level in old rats. Ann. NY. Acad. Sci. 1992, 673: 53–57.PubMedCrossRefGoogle Scholar
  16. 16.
    Anisimov V.N., Khavinson V.Kh., Mikhalski A.I., Yashin I. Effect of synthetic thymic and pineal peptides on biomarkers of ageing, survival and spontaneous tumour incidence in female CBA mice. Mech. Ageing Dev. 2001, 122: 41–68.PubMedCrossRefGoogle Scholar
  17. 17.
    Anisimov V.N., Arutjunyan A.V., Khavinson V.Kh. Effects of pineal peptide preparation epithalamin on free-radical processes in human and animals. Neuroendocrinol. Lett. 2001, 22: 9–18.PubMedGoogle Scholar
  18. 18.
    Khavinson V.Kh., Morozov V.G. Novel approaches to the prevention and treatment of age-associated pathology using peptide bioregulators — Epithalamin and thymalin. In: aging in the americas: frontiers of care, policy and research. Abstr. of Pan-American Congress, February 21–24, San Antonio, 1999, p. 46.Google Scholar
  19. 19.
    Goncharova N.D., Khavinson V.Kh., Lapin B.A. Regulatory effect of epithalon on production of melatonin and cortisol in old monkeys. Bull. Exp. Biol. Med. 2001, 131: 394–396.PubMedCrossRefGoogle Scholar
  20. 20.
    Khavinson V.Kh., Goncharova N., Lapin B. Synthetic tetrapeptide epitalon restores disturbed neuroendocrine regulation in senescent monkeys. Neuroendocrinol. Lett. 2001, 22: 251–254.PubMedGoogle Scholar
  21. 21.
    Zhao Z.Y., Touitou Y. Kinetic changes of melatonin release in rat pineal perifusion at different circadian stages. Effects of corticosteroids. Acta Endocrinol. 1993, 129: 81–88.PubMedGoogle Scholar
  22. 22.
    Zhao Z.Y., Touitou Y. Differences in isoproterenol-stimulated melatonin production by perifused rat pineal glands: Time dependent effects and role of enantiomeric forms. Life Sci. 1994, 54: 497–502.CrossRefGoogle Scholar
  23. 23.
    Fraser S., Cowen P., Franklin M., Franey C., Arendt J. Direct radioimmunoassay for melatonin in plasma. Clin. Chem. 1983, 29: 396–397.PubMedGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2003

Authors and Affiliations

  • Y. Djeridane
    • 1
  • V. Kh. Khavinson
    • 2
  • V. N. Anisimov
    • 2
  • Yvan Touitou
    • 1
  1. 1.Faculty of Medicine Pitié-SalpêtrièreMedical Biochemistry and Molecular BiologyParisFrance
  2. 2.Saint-Petersburg Institute of Bioregulation and GerontologySt. PetersburgRussia

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