Skip to main content
Log in

Input and output signals in a model neural system: The regulation of melatonin production in the pineal gland

  • Published:
In Vitro Aims and scope Submit manuscript

Summary

The production of melatonin has been studied using organ cultures of pineal glands incubated with methionine-methyl-3H. Melatonin-O-methyl-3H was extracted from cultured pineal glands and incubation media, and the activity of N-acetyltransferase was measured. This is the first of two enzymes necessary for the conversion of serotonin to melatonin in the pineal. The treatment of pineal glands with norepinephrine or dibutyryl cyclic AMP increased the release of melatonin-O-methyl-3H into the incubation media and the concentration of melatonin-O-methyl-3H in the glands. These treatments also resulted in the stimulation of N-acetyltransferase, as compared to untreated glands. The transduction of neural information to biochemical, signals which regulate the melatonin pathway appears to involve the release of norepinephrine, which stimulates N-acetyltransferase activity through an adenyl cyclase-cyclic AMP mechanism, as evidenced by these and other studies discussed.

In the present study the effects of harmine were studied. This hallucinogen is known to inhibit monoamine oxidase and stimulate melatonin production. Harmine was observed to stimulate N-acetyltransferase. This observation raises the possibility that an important action of this psychotropic drug may be on mechanisms which convert neural activity into biochemical events.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Wurtman, R. J., J. Axelrod, and D. Kelly. 1968.The Pineal. Academic Press, New York.

    Google Scholar 

  2. Reiter, R. J., and F. Fraschini. 1969. Endocrine aspects of the mammalian pineal gland: a review. Neuroendocrinology 5: 219–255.

    Article  PubMed  CAS  Google Scholar 

  3. Barchas, J. D., and A. B. Lerner. 1964. Localization of melatonin in the nervous system, J. Neurochem. 11: 489–492.

    Article  PubMed  CAS  Google Scholar 

  4. Axelrod, J., R. D. MacLean, R. W. Albers, and H. Weissbach. 1961. Regional distribution of methyl transferase enzymes in the nervous system and glandular tissues. S. S. Kety and J. Elkes, (Eds.),Regional Neurochemistry. Pergamon Press. Oxford. pp 307–311.

    Google Scholar 

  5. Axelrod, J., and H. Weissbach. 1961. Purification and properties of hydroxyindole-O-methyl transferase. J. Biol. Chem. 236: 211–215.

    PubMed  CAS  Google Scholar 

  6. Weissbach, H., B. G. Redfield, and J. Axelrod. 1961. The enzymatic acetylation of serotonin and other naturally occurring amines. Biochim, Biophys. Acta 54: 190–192.

    Article  CAS  Google Scholar 

  7. Weissbach, H., B. G. Redfield, and J. Axelrod. 1960. Biosynthesis of melatonin: enzymic conversion of serotonin to N-acetylserotonin. Biochim. Biophys. Acta 43: 352–353.

    Article  PubMed  CAS  Google Scholar 

  8. Neff, N. H., R. C. Lin, S. H. Ngai, and E. Costa. 1969. Turnover rate measurements of brain serotonin in unanesthetized rats. Advances. Biochem. Psychopharmacol. 1: 91–109.

    CAS  Google Scholar 

  9. Neff, N. H., R. E. Barret, and E. Costa. 1969. Kinetic and fluorescent histochemical analysis of the serotonin compartments in rat pineal gland. Eur. J. Pharmacol. 5: 348–356.

    Article  PubMed  CAS  Google Scholar 

  10. Quay, W. B., and A. Halevy. 1962. Experimental modification of the rat pineal's content of serotonin and related indole amines. Physiol. Zool. 35: 1–7.

    CAS  Google Scholar 

  11. Garattini, S., and L. Valzelli. 1965.Serotonin. Elsevier Publishing Company. Amsterdam.

    Google Scholar 

  12. Wurtman, R. J., F. Larin, J. Axelrod, H. M. Shein, and K. Rosasco. 1968. Formation of melatonin and 5-hydroxy indole acetic acid from14C-tryptophan by rat pineal glands in organ culture. Nature (London) 217: 953–954.

    Article  CAS  Google Scholar 

  13. Klein, D. C., and J. Rowe. 1970. Pineal gland in organ culture: Harmine inhibition of serotonin-14C oxidation is accompanied by stimulation of melatonin-14C production. Molec. Pharmacol. 6: 164–171.

    CAS  Google Scholar 

  14. Kappers, A. J. 1960. The development topographical relations and innervation of the epithysis cerebri in the albino rat. Z. Zellforsch. 52: 163–215.

    Article  PubMed  CAS  Google Scholar 

  15. Taylor, A. N., and R. W. Wilson. 1970. Electro-physiological evidence for the action of light on the pineal gland in the rat. Experientia 26: 267–269.

    Article  PubMed  CAS  Google Scholar 

  16. Reiter, R. J. 1967. The effect of pineal grafts, pinealectomy and denervation of the pineal gland on the reproductive organs of male hamsters. Neuroendocrinology. 2: 138–146.

    Article  Google Scholar 

  17. Reiter, R. J. 1968. The pineal gland and gonadal development in male rats and hamsters. Fertil. Steril. 19: 1009–1017.

    PubMed  CAS  Google Scholar 

  18. Reiter, R. J., S. D. Sorrentino, J. C. Hoffmann, and P. H. Rubin. 1968. Pineal, neural and photic control of reproductive organ size in early androgen-treated male rats. Neuroen-docrinology 3: 246.

    CAS  Google Scholar 

  19. Axelrod, J., R. J. Wurtman, and S. A. Snyder. 1965. Control of hydroxyindole-O-methyl-transferase activity in the rat pineal gland by environmental lighting. J. Biol. Chem. 240: 949–954.

    PubMed  CAS  Google Scholar 

  20. Klein, D. C. and J. L. Weller. Indole metabolism in the pineal gland: a circadian rhythm in N-acetyltransferase. Science, 169: 1093–1095.

  21. Axelrod, J., S. H. Snyder, A. Heller, and R. Y. Moore. 1966. Light-induced changes in pineal hydroxyindole-O-methyltransferase. Science 154: 898–899.

    Article  PubMed  CAS  Google Scholar 

  22. Moore, R. Y., A. Heller, R. J. Wurtman, and J. Axelrod. 1967. Visual pathway mediating pineal response to environmental light. Science 155: 220–223.

    Article  PubMed  CAS  Google Scholar 

  23. Moore, R. Y., A. Hellex, R. K. Bhatnaga, R. J. Wurtman, and J. Axelrod. 1968. Central control of the pineal gland: visual pathways. Arch. Neurol. 18: 208–218.

    PubMed  CAS  Google Scholar 

  24. Fiske, V. M. 1964. Serotonin rhythm in the pineal organ: control by the sympathetic nervous system. Science 146: 253–254.

    Article  PubMed  CAS  Google Scholar 

  25. Wolfe, D., L. Potter, K. Richardson, and J. Axelrod. 1962. Localizing tritiated norepi-nephrine in sympathetic axons by electron microscopic autoradiography. Science 138: 440–442.

    Article  PubMed  CAS  Google Scholar 

  26. Bondareff, W., and B. Gordon. 1966. Submicroscopic localization of norepinephrine in sympathetic nerves of rat pineal. J. Pharmacol. Exp. Ther. 153: 42–47.

    PubMed  CAS  Google Scholar 

  27. Peligrino de Iraldi, A., and L. M. Zieher. 1966. Central control of noradrenalin content in rat pineal and submaxillary glands. Life Sci. 5: 155–161.

    Article  Google Scholar 

  28. Axelrod, J., H. M. Shein, and R. J. Wurtman. 1969. Stimulation of C14-melatonin synthesis from C14 tryptophan by noradrenaline in rat pineal in organ culture. Proc. Nat. Acad. Sci. U. S. A. 62: 544–549.

    Article  CAS  Google Scholar 

  29. Klein, D. C. 1969. Pineal gland metabolism: The relationship between hydroxyindole-O-methyl transferase, melatonin production and secretion as stimulated by norepinephrine. Fed. Proc. 28: 734.

    Google Scholar 

  30. Weiss, B., and E. Costa 1967. Adenyl cyclase activity in rat pineal gland: Effects of chronic denervation and norepinephrine. Science 156: 1750–1752.

    Article  PubMed  CAS  Google Scholar 

  31. Weiss, B., and E. Costa. 1968. Selective stimulation of adenyl cyclase of rat pineal gland by pharmacologically active catecholamines. J. Pharmacol. Exp. Ther. 161: 310–319.

    CAS  Google Scholar 

  32. Butcher, R. W., G. A. Robison, J. G. Hardman, and E. W. Sutherland. 1967. The role of cyclic AMP in hormone action. Advances Enzym. Regulat. 6: 357–389.

    Article  Google Scholar 

  33. Shein, H. M., and R. J. Wurtman. 1969. Cyclic adenosine monophosphate: Stimulation of melatonin and serotonin synthesis in cultured rat pineals. Sciece 166: 519–520.

    Article  CAS  Google Scholar 

  34. Klein, D. C., G. R. Berg, J. Weller, and W. Glinsmann. 1970. Pineal gland: dibutyryl cyclic adenosine monophosphate stimulation of labeled melatonin production. Science 167: 1738–1740.

    Article  PubMed  CAS  Google Scholar 

  35. Klein, D. C., G. R. Berg, and J. Weller. 1970. Melatonin synthesis: adenosine 3′, 5′-mono-phosphate and norepinephrine stimulate N-acetyltransferase. Science 168: 979–980.

    Article  PubMed  CAS  Google Scholar 

  36. Trowell, O. A. 1959. The culture of mature organs in a sympathetic medium. Exp. Cell Res. 16: 118–147.

    Article  PubMed  CAS  Google Scholar 

  37. Raisz, L. G. 1965. Bone resorption in tissue culture. Factors influencing the response to parathyroid hormone. J. Clin. Invest. 44: 103–116.

    Article  PubMed  CAS  Google Scholar 

  38. Raisz, L. G., and I. Niemann. 1969. Effect of phosphate, calcium and magnesium on bone resporption and hormonal responses in tissue culture. Endocrinology 85: 446–452.

    Article  PubMed  CAS  Google Scholar 

  39. Klein, D. C., and A. Notides. 1969. Thin-layer chromatographic separation of pineal gland derivatives of serotonin-14C. Anal. Biochem. 31: 480–483.

    Article  PubMed  CAS  Google Scholar 

  40. Quay, W. B. 1964. Circadian and estrous rhythms in pineal melatonin and 5-hydroxy-indole-3-indole acetic acid. Proc. Soc. Exp. Biol. Med. 115: 710–713.

    PubMed  CAS  Google Scholar 

  41. Maickel, R. P., and F. P. Miller. 1968. The fluorometric determination of indolealkylamines in brian and pineal gland. Advances Pharmacol. 6A: 71–77.

    Article  Google Scholar 

  42. Berg. G. R., and D. C. Klein. Unpublished observations.

  43. Weiss, B., and A. D. Kidman. 1969. Neurobiological significance of cyclic 3′,5′-adenosine monophosphate. Advances Biochem. Psychopharmacol. 1: 131–164.

    CAS  Google Scholar 

  44. Snyder, S. H., J. Axelrod, J. E. Fisher, and R. J. Wurtman. 1964. Neural and photic regulation of 5-hydroxytryptophan decarboxylase in the rat pineal gland. Nature (London) 203:981–982.

    Article  CAS  Google Scholar 

  45. Snyder, S. H., M. Zweig, J. Axelrod, and J. E. Fischer. 1965. Control of the circadian rhythm in serotonin content of the rat pineal gland. Proc. Nat. Acad. Sci. U.S.A. 53: 301–305.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Klein, D.C., Weller, J. Input and output signals in a model neural system: The regulation of melatonin production in the pineal gland. In Vitro 6, 197–204 (1970). https://doi.org/10.1007/BF02617764

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02617764

Keywords

Navigation