Melatonin: Reproductive Effects

  • R. J. Reiter
  • M. D. Rollag
  • Elizabeth S. Panke
  • A. F. Banks
Conference paper
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 13)


N-acetyl-5-methoxytryptamine, melatonin, is synthesized within and secreted from the pineal gland. Although the concentration of this constituent in the blood is diminished after surgical removal of the pineal gland it does not completely disappear. Other potential contributors to blood titers of melatonin include the retinas, the Harderian glands and the gastrointestinal tract. Melatonin has a potent antigonadotrophic action in the Syrian hamster (a highly photosensitive species) provided the indole is given during a restricted portion of the light phase of the light-dark cycle. This so-called sensitive period falls late in the light phase; melatonin acutely administered at other times has virtually no inhibitory influence on the reproductive physiology of hamsters. When melatonin is continuously available (from a subcutaneous deposit) it counteracts the antigonadotrophic influence of the pineal gland in light restricted or blinded hamsters, i.e., it causes a “functional pinealectomy”. Furthermore, chronically available melatonin negates the antigonadotrophic capability of acute melatonin injections.


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  1. Axelrod, J., Weissbach, H.: Purification and properties of hydroxyindole-O-methyltransferase. J. Biol. Chem. 236, 211–213 (1961).PubMedGoogle Scholar
  2. Axelrod, J., Mac Lean, P. D., Albers, R. W., Weissbach, H.: Regional distribution of methyl transferase enzymes in the nervous system and glandular tissues. In: Regional Neurochemistry (Kety, S. S., Elkes, J., eds.), p. 301. New York: Pergamon. 1961.Google Scholar
  3. Brown, G. M., Basinska, J., Bubenik, G., Sibony, D., Grota, L. J., Siancer, H. C.: Gonadal effects of pinealectomy and immunization against N-acetylindolealkylamines in the hamsters. Neuroendocrinology 22, 289–297 (1976).CrossRefPubMedGoogle Scholar
  4. Bubenik, G. A., Brown, G. M., Grota, L. J.: Differential localization of N-acetylated indolealkylamines in CNS and the Harderian gland using immunohistology. Brain Res. 118, 417–427 (1976 a).CrossRefPubMedGoogle Scholar
  5. Bubenik, G. A., Brown, G. M., Grota, L. J.: Immunohistochemical localization of melatonin in the rat harderian gland. J. Histochem. Cytochem. 24, 1173–1177 (1976b).CrossRefPubMedGoogle Scholar
  6. Bubenik, G. A., Brown, G. M., Grota, L. J.: Immunohistological localization of melatonin in the rat digestive system. Experientia 33, 662–663 (1977).CrossRefPubMedGoogle Scholar
  7. Cardinali, D. P.: Melatonin and the endocrine role of the pineal gland. In: Current Topics in Experimental Endocrinology, Vol. 2 (James, V. H. T., Martini, L., eds.), p. 107. New York: Academic Press. 1974.Google Scholar
  8. Cardinali, D. P., Rosner, J. M.: Retinal localization of the hydroxyindole-O-methyl transferase (HIOMT) in the rat. Endocrinology 89, 301–303 (1971 a).CrossRefPubMedGoogle Scholar
  9. Cardinali, D. P., Rosner, J. M.: Metabolism of serotonin by the rat retina in vitro. J. Neurochem. 18, 1769–1770 (1971 b).CrossRefPubMedGoogle Scholar
  10. Cardinali, D. P., Wurtman, R. J.: Hydroxyindole-O-methyl transferases in rat pineal, retina and Harderian gland. Endocrinology 91, 247–252 (1972).CrossRefPubMedGoogle Scholar
  11. Cardinali, D. P., Larin, F., Wurtman, R. J.: Action spectra for effects of light on hydroxyindole-O-methyl transferases in rat pineal, retina and Harderian gland. Endocrinology 91, 877–886 (1972).CrossRefPubMedGoogle Scholar
  12. Gaston, S., Menaker, M.: Photoperiodic control of hamster testis. Science 158, 925–927 (1967).CrossRefPubMedGoogle Scholar
  13. Hoffmann, K.: Testicular involution in short photoperiods inhibited by melatonin. Naturwissenschaften 61, 364–365 (1974).CrossRefPubMedGoogle Scholar
  14. Kennaway, D. J., Frith, R. G., Phillipou, G., Matthews, C. D., Seamark, R. F.: A specific radioimmunoassay for melatonin in biological tissue and fluids and its validation by gas chromatography-mass spectro-metry. Endocrinology 101, 119–127 (1977).CrossRefPubMedGoogle Scholar
  15. Kinson, G. A.: Pineal factors in the control of testicular function. Adv. Sex Horm. Res. 2, 87–139 (1976).PubMedGoogle Scholar
  16. Knigge, K. M., Sheridan, M. N.: Pineal function in hamsters bearing meiatonin antibodies. Life Sci. 19, 1235–1238 (1976).CrossRefPubMedGoogle Scholar
  17. Koslow, S. H.: 5-Methoxytryptamine: A possible central nervous system transmitter. Adv. Biochem. Psychopharm. 11, 95–98 (1974).Google Scholar
  18. Minneman, K. P., Wurtman, R. J.: Effect of pineal compounds of mammals. Life Sci. 17, 1189–1200 (1975).CrossRefPubMedGoogle Scholar
  19. Nagle, C. A., Cardinali, D. P., Rosner, J. M.: Light regulation of rat retinal hydroxyindole-O-methyl transferase (HIOMT) activity. Endocrinology 91, 423–426 (1972).CrossRefPubMedGoogle Scholar
  20. Nagle, C. A., Cardinali, D. P., Rosner, J. M.: Retinal and pineal hydroxyindole-O-methyl transferases; in the rat: Changes following cervical sympathectomy, pinealectomy or blinding. Endocrinology 92, 1560 to 1564 (1973).CrossRefPubMedGoogle Scholar
  21. Nagle, C. A., Cardinali, D. P., Rosner, J. M.: Effects of castration and testosterone administration on pineal and retinal hydroxyindole-O-methyl transferase of male rats. Neuroendocrinology 14, 14–23 (1974).CrossRefPubMedGoogle Scholar
  22. Ozaki, Y., Lynch, H. J.: Presence of melatonin in plasma and urine of pinealectomized rats. Endocrinology 99, 641–644 (1976).PubMedGoogle Scholar
  23. Pang, S. F., Ralph, C. L.: Pineal and serum melatonin at midday and midnight following pinealectomy or castration in male rats. J. Exp. Zool. 193, 275–280 (1975).CrossRefPubMedGoogle Scholar
  24. Pang, S. F., Brown, G. M., Grota, L. J., Chambers, J. W., Rodman, R. L.: Determination of N-acetylserotonin and melatonin activities in the pineal gland, retina, Harderian gland, brain and serum of rats and chickens. Neuroendocrinology 23, 1–13 (1977).CrossRefPubMedGoogle Scholar
  25. Quay, W. B.: Pineal Chemistry. Springfield: Ch. C Thomas. 1974.Google Scholar
  26. Raikhlin, N. T., Kvetnoy, I. M., Tolkachev, V. N.: Melatonin may be synthesized in enterochromaffin cells. Nature 225, 344–345 (1975).CrossRefGoogle Scholar
  27. Reiter, R. J.: The role of the pineal in reproduction. In: Reproductive Biology (Balin, H., Glasser, S., eds.), p. 71. Amsterdam: Excerpta Medica. 1972.Google Scholar
  28. Reiter, R. J.: Comparative physiology: Pineal gland. Ann. Rev. Physiol. 35, 305–328 (1973).CrossRefGoogle Scholar
  29. Reiter, R. J.: The Pineal—1977. Montreal: Eden Press. 1977.Google Scholar
  30. Reiter, R. J., Vaugban, M. K., Blask, D. E., Johnson, L. Y.: Melatonin: Its inhibition of pineal antigonadotrophic activity in male hamsters. Science 185, 1169–1171 (1974).CrossRefPubMedGoogle Scholar
  31. Reiter, R. J., Vaugban, M. K., Vaughan, G. M., Sorrentino, S., jr., Donofrio, R. J.: The pineal gland as an organ of internal secretion. In: Frontiers of Pineal Physiology (Altschule, M. D., ed.), p. 54. Cambridge: MIT Press. 1975 a.Google Scholar
  32. Reiter, R. J., Vaugban, M. K., Waring, P. J.: Studies on the minimal dosage of melatonin required to inhibit pineal antigonadotrophic activity in male golden hamsters. Horm. Res. 6, 258–267 (1975 b).CrossRefPubMedGoogle Scholar
  33. Reiter, R. J., Blask, D. E., Johnson, L. Y., Rudeen, P. K., Vaughan, M. K., Waring, P. J.: Melatonin inhibition of reproduction in the male hamster; its dependency on time of day of administration and on an intact and sympathetically innervated pineal gland. Neuroendocrinology 22, 107 to 116 (1976 a).CrossRefPubMedGoogle Scholar
  34. Reiter, R. J., Rudeen, P. K., Vaughan, M. K.: Restoration of fertility in light-deprived female hamsters by chronic melatonin treatment. J. Comp. Physiol. 111, 7–13 (1976 b).CrossRefGoogle Scholar
  35. Reiter, R. J., Rudeen, P. K., Sackman, J. W., Vaughan, M. K., Johnson, L. Y., Little, J. C.: Subcutaneous melatonin implants inhibit reproductive atrophy in male hamsters induced by daily melatonin injections. Endocr. Res. Commun. 4, 35–44 (1977).CrossRefPubMedGoogle Scholar
  36. Relkin, R.: Rat pituitary and plasma prolactin levels after pinealectomy. J. Endocr. 53, 179–180 (1972).CrossRefPubMedGoogle Scholar
  37. Tamarkin, L., Brown, S., Goldman, B.: Neuroendocrine regulation of seasonal reproductive cycles in the hamster. Abstr. 5th Ann. Mtg. Soc. Neuroscience, p. 458 (1975).Google Scholar
  38. Tamarkin, L., Westrom, W. K., Ramili, A. I., Goldman, B. D.: Effect of melatonin on the reproductive systems of male and female Syrian hamsters: A diurnal rhythm in sensitivity to melatonin. Endocrinology 99, 1534–1541 (1976).CrossRefPubMedGoogle Scholar
  39. Vlahakes, G. J., Wurtman, R. J.: A Mg2+ dependent hydroxyindole-O-methyltransferase in rat harderian gland. Biochim. Biophys. Acta 261, 194–198 (1972).CrossRefPubMedGoogle Scholar
  40. Wurtman, R. J., Axelrod, J., Chu, E. W.: Melatonin, a pineal substance: Effect on rat ovary. Science 141, 277–278 (1963).CrossRefPubMedGoogle Scholar
  41. Wurtman, R. J., Kelly, D. E., Axelrod, J.: The pineal. New York: Academic Press. 1968 a.Google Scholar
  42. Wurtman, R. J., Larin, F., Axelrod, J., Shein, H. M., Rosasco, K.: Formation of melatonin and 5-hydroxyindole acetic acid from 14C-tryptophan by rat pineal glands in organ culture. Nature 217, 953–954 (1968 b).CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 1978

Authors and Affiliations

  • R. J. Reiter
    • 1
  • M. D. Rollag
    • 1
  • Elizabeth S. Panke
    • 1
  • A. F. Banks
    • 1
  1. 1.Department of AnatomyThe University of Texas Health Science Center at San AntonioSan AntonioUSA

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