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The melatonin rhythm: both a clock and a calendar

  • Multi-Author Reviews
  • Melatonin and the Light-Dark Zeitgeber in Vertebrates, Invertebrates and Unicellular Organisms
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Abstract

The paper briefly reviews the data which shows that the circadian production and secretion of melatonin by the pineal gland can impart both daily, i.e., clock, and seasonal, i.e., calendar, information to the organism. The paper summarizes the 3 patterns of nocturnal melatonin production that have been described. Clearly, regardless of the pattern of nocturnal melatonin production a particular species normally displays, the duration of nightime elevated melatonin is proportional to the duration of the night length. Since daylength under natural conditions changes daily the melatonin rhythm, which adjusts to the photoperiod sends time of year information to the organism. The melatonin receptors which subserve the clock message sent by the pineal gland in the form of a melatonin cycle may reside in the biological clock itself, namely, the suprachiasmatic nuclei (SCN). The melatonin receptors that mediate seasonal changes in reproductive physiology are presumably those that are located on the pars tuberalis cells of the anterior pituitary gland. Besides these receptors which likely mediate clock and calendar information, melatonin receptors have been described in other organs. Interestingly, the distribution of melatonin receptors is highly species-specific. Whereas the clock and calendar information that the melatonin cycle imparts to the organism relies on cell membrane receptors, a fact that is of some interest considering the high lipophilicity of melatonin, recent studies indicate that other functions of melatonin may require no receptor whatsoever.

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References

  1. Arendt, J., Mammalian pineal rhythms. Pineal Res. Rev.3 (1985) 161–213.

    Google Scholar 

  2. Arendt, J., Aldhous, M., English, J., Marks, V., and Arendt, J. H., Some effects of jet lag and their alleviation by melatonin. Ergonomics30 (1987) 1379–1386.

    Google Scholar 

  3. Armstrong, S. M., and Redman, J., Melatonin: A chronobiotic with anti-aging properties. Med. Hypotheses34 (1991) 300–309.

    PubMed  Google Scholar 

  4. Berga, S. L., Mortola, J. F., and Yen, S. S. C., Amplification of noctural melatonin secretion in women with functional amenorrhea. J. clin. Endocr. Metab.66 (1988) 242–244.

    PubMed  Google Scholar 

  5. Binkley, S. A., Pineal and melatonin: Circadian rhythms and body temperature of sparrows, in: Chronobiology, pp. 582–585. Eds L. E. Scheving, F. Halberg, J. Pasley and E. Grades. Shoin Press, Tokyo 1974.

    Google Scholar 

  6. Bittman, E. L., and Karsch, F. J., Nightly duration of pineal melatonin secretion determines the reproductive response to inhibitory daylength in the ewe. Biol. Reprod.30 (1984) 585–593.

    PubMed  Google Scholar 

  7. Brainard, G. C. Jr., Peterborg, L. J., Richardson, B. A., and Reiter, R. J., Pineal melatonin in Syrian hamsters: Circadian and seasonal rhythms in animals maintained under laboratory and natural conditions. Neuroendocrinology35 (1982) 342–348.

    PubMed  Google Scholar 

  8. Carter, D. S., and Goldman, B. D., Antigonadal effects of timed melatonin infusion in pinealectomized male Djungarian hamsters (Phodopus sungorus): Duration is the critical parameter. Endocrinology113 (1983) 1268–1273.

    PubMed  Google Scholar 

  9. Carter D. S., Hall, V. D., Tamarkin, L., and Goldman, B. D., Pineal is required for testicular maintenance in the Turkish hamster (Mesocricetus brandti). Endocrinology111 (1982) 863–871.

    PubMed  Google Scholar 

  10. Daya, S., Nonaka, K. O., Buzzell, G. R., and Reiter, R. J., Heme precursor 5-aminolevulinic acid alters brain tryptophan and serotonin levels without changing pineal serotonin and melatonin levels. J. Neurosci. Res.23 (1989) 304–310.

    PubMed  Google Scholar 

  11. Delgado, M. J., and Vivien-Roels, B., Effect of environmental temperature and photoperiod on melatonin levels in the pineal, lateral eye, and plasma of frog,Rana perezi: Importance of ocular melatonin. Gen. comp. Endocr.75 (1989) 46–53.

    PubMed  Google Scholar 

  12. Erskine, D. J., and Hutchinson, V. H., Melatonin and behavioral thermoregulation in the turtle,Terrapene carolina triunguis. Physiol. Behav.26 (1981) 991–994.

    PubMed  Google Scholar 

  13. Gern, W. A., Duvall, D., and Nervina, J. M., Melatonin: A discussion of its evaluation and actions in vertebrates. Am. Zool.26 (1986) 985–996.

    Google Scholar 

  14. Gillette, M. V., and Prosser, R. A., Melatonin directly resets the rat suprachiasmatic circadian clock in vitro. Brain Res.565 (1991) 158–161.

    PubMed  Google Scholar 

  15. Gittes, R. F., and Chu, E. W., Reversal of the effect of pinealectomy in female rats by multiple isogeneic pineal transplants. Endocrinology77 (1965) 1061–1067.

    PubMed  Google Scholar 

  16. Goldman, B. D., The physiology of melatonin in mammals. Pineal Res. Rev.1 (1983) 145–182.

    Google Scholar 

  17. Goto, M., Oshima, I., Tomita, T., and Ebihara, S., Melatonin content of the pineal gland in different mouse strains. J. Pineal Res.7 (1989) 195–203.

    PubMed  Google Scholar 

  18. Hoffman, R. A., and Reiter, R. J., Pineal gland: Influence on gonads of male hamsters. Science148 (1965) 1609–1611.

    PubMed  Google Scholar 

  19. Hoffmann, K., Illnerova, H., and Vanecek, J., Change in the duration of the nighttime melatonin peak may be a signal driving photoperiodic response in the Djungarian hamster (Phodopus sungorus). Neurosci. Lett.56 (1985) 39–43.

    PubMed  Google Scholar 

  20. Honma, S., Kanematsu, N., Katsuno, Y., and Honma, K.-I., Light suppression of nocturnal pineal and plasma melatonin in rats depends on wavelength and time of day. Neurosci. Lett.147 (1992) 201–204.

    PubMed  Google Scholar 

  21. Huether, G., Poeggeler, B., Reimer, A., and George, A., Effect of tryptophan administration on circulating melatonin levels in chicks and rats: Evidence for stimulation of melatonin synthesis and release in the gastrointestinal tract. Life Sci.51 (1992) 945–953.

    PubMed  Google Scholar 

  22. Kennaway, D. J., and Van Dorp, C. F., Free running rhythms of melatonin, cortisol, electrolytes and sleep in humans in Antarctica. Am. J. Physiol.260 (1991) R1137-R1144.

    PubMed  Google Scholar 

  23. Legan, S. J., and Karsch, F. J., Neuroendocrine regulation of the estrous cycle and seasonal breeding in the ewe. Biol. Reprod.20 (1979) 74–85.

    PubMed  Google Scholar 

  24. Lerner, A. B., Case, J. D., Takahashi, Y., Lee, T. H., and Mori, W., Isolation of melatonin, the pineal factor that lightens melanocytes. J. Am. Chem. Soc.80 (1958) 2587.

    Google Scholar 

  25. Lewy, A. J., and Newsom, D. A., Different types of melatonin circadian rhythms in some blind subjects. J. clin. Endocr. Metab.56 (1983) 1103–1107.

    PubMed  Google Scholar 

  26. Lewy, A. J., and Sack, R. L., Light therapy and psychiatry. Proc. Soc. exp. Biol. Med.183 (1986) 11–18.

    PubMed  Google Scholar 

  27. Lincoln, G. A., and Short, R. V. Seasonal breeding: Nature's contraceptive. Recent Prog. Horm. Res.36 (1980) 1–52.

    PubMed  Google Scholar 

  28. McConnell, S. J., and Ellendorf, F., Absence of nocturnal plasma melatonin surges under long and short artificial photoperiods in domestic sow. J. pineal Res.5 (1987) 295–308.

    Google Scholar 

  29. McIntyre, I. M., Norman, T. R., Burrows, G. D., and Armstrong, S. M., Melatonin rhythm in human plasma and saliva. J. Pineal Res.4 (1987) 117–183.

    Google Scholar 

  30. Meijer, J. H., Integration of visual information by suprachiasmatic nuclei, in: Suprachiasmatic Nucleus, Eds. D. C. Klein, R. Y. Moore and S. M. Reppert, pp. 107–119. Oxford University Press, Oxford 1991.

    Google Scholar 

  31. Michel, S., Geusz, M. E., Zaritsky, J. J., and Block, G. D., Circadian rhythm in membrane conductance expressed in isolated neurons. Science259 (1993) 239–241.

    PubMed  Google Scholar 

  32. Morgan, P. J., and Williams, L. M., Central melatonin receptors: Implications for a mode of action. Experientia45 (1989) 955–965.

    PubMed  Google Scholar 

  33. Nagakawa, H., Sack, R. G., and Lewy, A. J., Sleep propsensity free-runs with the temperature, melatonin and cortisol rhythms in a totally blind person. Sleep15 (1992) 330–336.

    PubMed  Google Scholar 

  34. Palm, L., Blennow, G., and Wetterberg, L., Correction of non-24-hour sleep/wake cycle by melatonin in a blind retarded boy. Ann. Neurol.29 (1991) 336–339.

    PubMed  Google Scholar 

  35. Podolin, P. L., Rollag, M. D., and Brainard, G. E., The suppression of nocturnal pineal melatonin in Syrian hamster: Dose response curves at 500 and 360 nm. Endocrinology121 (1988) 266–270.

    Google Scholar 

  36. Poeggeler, B., Balzer, I., Hardeland, R., and Lerchl, A., Pineal hormone melatonin oscillates also in the dinoflagellateGonyaulaux polyedra. Naturwissenschaften78 (1991) 268–269.

    Google Scholar 

  37. Poeggeler, B., Reiter, R. J., Tan, D.-X., Chen, L.-D., and Manchester, L. C. Melatonin, hydroxyl radical mediated oxidative damage and aging: A hypothesis. J. Pineal Res.14 (1993) 151–168.

    PubMed  Google Scholar 

  38. Quay, W. B., Circadian rhythm in rat pineal serotonin and its modification by estrous cycle and photoperiod. Gen. comp. Endocr.3 (1963) 473–479.

    Google Scholar 

  39. Rawding, R. S., and Hutchinson, V. H., Influence of temperature and photoperiod on plasma melatonin in the mudpuppyNecturus maculosus. Gen. comp. Endocr.88 (1992) 364–373.

    PubMed  Google Scholar 

  40. Reiter, R. J., The effect of pineal grafts, pinealectomy and denervation of the pineal gland on the reproductive organs of male hamsters. Neuroendocrinology2 (1967) 138–146.

    Google Scholar 

  41. Reiter, R. J., Pineal control of a seasonal reproductive rhythm in golden hamsters exposed to natural daylength and temperature. Endocrinology92 (1973) 423–430.

    PubMed  Google Scholar 

  42. Reiter, R. J., Circannual reproductive rhythms in mammals related to photoperiod and pineal functions: A review. Chronobiologia1 (1974) 365–395.

    PubMed  Google Scholar 

  43. Reiter, R. J., The pineal and its hormones in the control of reproduction in mammals. Endocrine Rev.1 (1980) 109–131.

    Google Scholar 

  44. Reiter, R. J., Reproductive involution in male hamsters exposed to naturally increasing daylengths after the winter solstice. Proc. Soc. exp. Biol. Med.163 (1980) 264–266.

    Google Scholar 

  45. Reiter, R. J., Action spectra, dose-response relationships and temporal aspects of light's effect on the pineal gland. Ann. N.Y. Acad. Sci.453 (1989) 215–230.

    Google Scholar 

  46. Reiter, R. J., The pineal gland: Reproductive interactions, in: Vertebrate Endocrinology: Fundamentals and Biomedical Implications, Vol. 4, Part B, Eds M. Schreibman and P. K. T. Pang, pp. 269–310. Academic Press, New York 1991.

    Google Scholar 

  47. Reiter, R. J., Pineal Gland: Interface between the photoperiodic environment and the endocrine system. Trends Endocr. Metab.2 (1991) 13–19.

    Google Scholar 

  48. Reiter, R. J., Pineal melatonin: Cell biology of its synthesis and of its physiological interactions. Endocrine Rev.12 (1991) 151–180.

    Google Scholar 

  49. Reiter, R. J., Melatonin: The chemical expression of darkness. Molec. cell. Endocr.79 (1991) C153-C159.

    PubMed  Google Scholar 

  50. Reiter, R. J. Alterations of the circadian melatonin rhythm by the electromagnetic spectrum: A study in environmental toxicology. Regul. Toxic. Pharmac.15 (1992) 226–244.

    Google Scholar 

  51. Reiter, R. J., The mammalian pineal gland as an end organ of the visual system, in: Light and Biological Rhythms. Eds L. Wetterberg and D. Ottosen, Karolinska Press, Stockholm, in press.

  52. Reiter, R. J., Britt, J. H., and Armstrong, J. D., Absence of nocturnal rise in either norepinephrine, N-acetyltransferase, hydroxyindole-O-methyltransferase, or melatonin in the pineal gland of the domestic pig kept under natural environmental photoperiods. Neurosci. Lett.81 (1987) 171–174.

    PubMed  Google Scholar 

  53. Reiter, R. J., Guerrero, J. M., and Santana, C., Nocturnal increase in pineal melatonin production in two lemming species,Decrostonyx hudsonius andD. groelandicus. Gen. comp. Endocr.78 (1990) 322–325.

    PubMed  Google Scholar 

  54. Reiter, R. J., and Hester, R. J., Interrelationships of the pineal gland, the superior cervical ganglia, and the photoperiod in the regulation of the endocrine systems of hamsters. Endocrinology79 (1966) 1168–1170.

    PubMed  Google Scholar 

  55. Reiter, R. J., Joshi, B. N., Heinzeller, T., and Nürnberger, F., A single 1- or 5-second light pulse at night inhibits rat [ineal melatonin. Endocrinology118 (1986) 1906–1909.

    PubMed  Google Scholar 

  56. Reiter, R. J., Poeggeler, B., Tan, D.-X., Chen, L.-D., and Manchester, L. C., Antioxidant capacity of melatonin: A novel function not requiring a receptor. Neuroendocr. Lett.15 (1993) 103–116.

    Google Scholar 

  57. Reiter, R. J., and Richardson, B. A., Static magnetic field effects on pineal indoleamine metabolism and possible biological consequences. FASEB J.6 (1992) 2283–2287.

    PubMed  Google Scholar 

  58. Reiter, R. J., White, T., Lerchl, A., Stokkan, K.-A., and Rodriquez, C., Attenuated nocturnal rise in pineal and serum melatonin in a genetically cardiomyopathic Syrian hamster with a deficient calcium pump. J. Pineal Res.11 (1991) 156–162.

    PubMed  Google Scholar 

  59. Repert, S. M., Weaver, D. R., Rivkees, S. A., and Stopa, E. G., Putative melatonin receptors in a human biological clock. Science242 (1988) 78–81.

    PubMed  Google Scholar 

  60. Robinson, J. E., Photoperiodic and steroidal regulation of the luteinzing hormone pulse generator in ewes, in: The Episodic Secretion of Hormones. Eds W. F. Crowley, Jr., and J. G. Hofler, pp. 159–167. John Wiley, New York 1987.

    Google Scholar 

  61. Rosenthal, N. S., Sack, D. A., Gillin, J. C., Lewy, A., Goodwin, F. K., Davenport, Y., Mueller, P. S., Newsome, D. A., and Wehr, T. A., Seasonal affective disorder. Archs Gen. Psychiat.41 (1984) 72–80.

    Google Scholar 

  62. Rudeen, P. K., Reiter, R. J., and Vaughan, M. K., Pineal serotonin N-acetyltransferase in four mammalian species. Neurosci. Lett.1 (1975) 225–229.

    Google Scholar 

  63. Santana, C., Guerrero, J. M., and Reiter, R. J., Effects of either forskolin or the 1,9-dideoxy derivative of forskolin on 8-bromocyclic AMP on cyclic AMP and melatonin production in the Syrian hamster pineal gland in organ culture. Neurosci. Lett.103 (1989) 338–342.

    PubMed  Google Scholar 

  64. Santana, C., Menendez-Pelaez, A., Reiter, R. J., and Guerrero, J. M., Treatment with forskolin for 8 hours during the day increases melatonin synthesis in the Syrian hamster pineal gland in organ culture: The long lag period is required for RNA synthesis. J. Neurosci. Res.25 (1990) 545–551.

    PubMed  Google Scholar 

  65. Stankov, B., Fraschini, F., and Reiter, R. J., Melatonin binding sites in the central nervous system. Brain Res. Rev.16 (1991) 245–256.

    PubMed  Google Scholar 

  66. Stetson, M. H., and Tate-Ostroff, B., Hormonal regulation of the annual reproductive cycle of golden hamsters. Gen. comp. Endocr.45 (1981) 329–344.

    PubMed  Google Scholar 

  67. Stetson, M. H., and Watson-Whitmyre, M., Effects of exogenous and endogenous melatonin on gonadal function in hamsters. J. neural Transm., Suppl.21 (1986) 55–80.

    Google Scholar 

  68. Sugden, D., Melatonin biosynthesis in the mammalian pineal gland. Experientia45 (1989) 922–932.

    PubMed  Google Scholar 

  69. Sun, J. H., Yaga, K., Reiter, R. J., Garza, M., Manchester, L. C., Tan, D.-X., and Poeggeler, B., Reduction in pineal N-acetyltransferase activity and pineal and serum melatonin levels in rats after their exposure to red light at night. Neurosci. Lett.149 (1993) 56–58.

    PubMed  Google Scholar 

  70. Tamarkin, L., Baird, C. J., and Almeida, O. F. X., Melatonin: A coordinating signal for mammalian reproduction? Science27 (1985) 714–720.

    Google Scholar 

  71. Tamarkin, L., Westrom, W. K., Hamill, A. I., and Goldman, B. D., Effect of melatonin on the reproductive systems of male and female Syrian hamsters: Diurnal rhythm in sensitivity to melatonin. Endocrinology99 (1976) 1534–1541.

    PubMed  Google Scholar 

  72. Tedesco, S. C., Flood, P. F., Morton, D. J., and Reiter, R. J., Seasonal melatonin and luteinizing hormone rhythms in muskoxen at 52° N. Rangifer12 (1992) 197–201.

    Google Scholar 

  73. Troiani, M. E., Reiter, R. J., Tannenbaum, M. G., Puig-Domingo, M., Guerrero, J. M., and Menendez-Pelaez, A., Neither the pituitary gland nor the sympathetic nervous system is responsible for eliciting the large drop in elevated rat pineal melatonin levels due to swimming. J. neural Transm.47 (1987) 55–60.

    Google Scholar 

  74. Underwood, H., Vertebrate circadian and photperiodic systems: Role of pineal gland and melatonin. J. biol. Rhythms2 (1987) 279–315.

    PubMed  Google Scholar 

  75. Underwood, H., The pineal and melatonin: Regulators of circadian function in lower vertebrates. Experientia46 (1990) 120–128.

    PubMed  Google Scholar 

  76. Vanecek, J., Poulik, A., and Illnerova, H., Hypothalamic melatonin receptor sites revealed by autoradiography. Brain Res.435 (1987) 359–362.

    PubMed  Google Scholar 

  77. Vivien-Roels, B., and Pevet, P., The pineal gland and the synchronization of reproductive cycles with variations of the environmental climatic conditions, with special reference to temperature. Pineal Res. Rev.1 (1983) 91–144.

    Google Scholar 

  78. Vivien-Roels, B., Pevet, R., and Claustrat, B., Pineal and circulating melatonin rhythms in the box turtle,Terrapene carolina triunguis: Effect of photoperiod, light pulse, and environmental temperature. Gen. comp. Endocr.69 (1988) 163–173.

    PubMed  Google Scholar 

  79. Voordouw, B. C. G., Euser, R., Verdonk, R. E. R., Alberda, B. Th., deJong, F. H., Drogendijk, A. C., Fauser, B. C. J. M., and Cohen, M., Melatonin and melatonin-progestin combinations alter pituitary-ovarian function in women and can inhibit ovulation. J. clin. Endocr. Metab.74 (1992) 108–117.

    PubMed  Google Scholar 

  80. Waldhauser, F., and Rietzel, M., Daily and annual rhythms in human melatonin secretion: Role in puberty control. Ann. N. Y. Acad. Sci.435 (1985) 205–214.

    Google Scholar 

  81. Webb, S. M., Champney, T. H., Lewinski, A. K., and Reiter, R. J., Photoreceptor damage and eye pigmentation: Influence on the sensitivity of rat pinealN-acetyltransferase activity and melatonin levels to light at night. Neuroendocrinology40 (1985) 205–209.

    PubMed  Google Scholar 

  82. Wehr, T. A., The duration of human melatonin secretion and sleep response to changes in daylength (photoperiod). J. clin. Endocr. Metab.73 (1991) 1276–1280.

    PubMed  Google Scholar 

  83. Wu, W., Scott, D. E., and Reiter, R. J., No difference in day-night serum melatonin concentration after pineal grafting into the third cerebral ventride of pinealectomized rats. J. Pineal Res.11 (1991) 70–74.

    PubMed  Google Scholar 

  84. Wurtman, R. J., Axelrod, J., and Phillips, L. S., Melatonin synthesis in the pineal gland: Control by light. Science142 (1963) 1071–1072.

    PubMed  Google Scholar 

  85. Yaga, K., Tan, D.-X., Reiter, R. J., Manchester, L. C., and Hattori, A. Unusual responses to nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms. J. Pineal Res.14 (1993) 98–103.

    PubMed  Google Scholar 

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Reiter, R.J. The melatonin rhythm: both a clock and a calendar. Experientia 49, 654–664 (1993). https://doi.org/10.1007/BF01923947

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