Summary
Daily rhythms in pineal methoxyindole metabolism have been described in rodents and humans: serotonin levels in rat pineals are highest during the daylight hours and fall markedly soon after the onset of darkness, coincident with increases in the levels of pineal melatonin and 5-methoxy-tryptophol and the activities of pineal serotonin-N-acetyltransferase (SNAT) and hydroxyindole-O-methyltransferase (HIOMT). The fact that the levels of melatonin and 5-methoxytryptophol vary in parallel suggests that the major factor generating the methoxyindole rhythms is not SNAT activity, as has been suggested, but a proximal step, perhaps a change in the availability (for metabolism) of “stored” serotonin. Melatonin levels in human serum and urine exhibit rhythms similar to those observed in rats, i.e., they rise sharply during the daily dark period. When the onset of darkness is delayed by 12 hours, human melatonin rhythms usually require 3 or 4 days to adjust to the new lighting regimen.
Environmental factors, other than light, that activate the sympathetic nervous system or cause epinephrine to be secreted from the adrenal medulla (e.g., the stress of immobilization; insulin-induced hypoglycemia) can override the inhibitory effects of light and accelerate melatonin synthesis. Melatonin levels in rat blood and urine are lowest during the proestrous and estrous phases of the estrous cycle. Although this effect of the ovarian steroid hormones is accompanied by a reduction in urinary norepinephrine levels, it is not caused simply by a decrease in the quantity of norepinephrine acting on the pineal but also involves a direct action of the hormones.
Ovariectomy increases serum melatonin levels, whereas the administration of estradiol plus progesterone (to ovariectomized animals) lowers melatonin levels.
The spectral and intensity-response characteristics of the photic inhibition of melatonin synthesis have been established for the rat. Rhythms in melatonin synthesis apparently persist among animals placed in environments of continuous darkness; the source of the cyclic signal (mediated by the pineal sympathetic nerves) has not yet been identified.
Preliminary evidence suggests that levels of a peptide hormone, arginine vasotocin, in rat pineals and sera also exhibit daily rhythms and are increased by norepinephrine.
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References
Arendt, J., Pannier, L., Sizonenko, P. C.: Melatonin radioimmunoassay. J. Clin. Endocrinol. Metab. 40, 347–350 (1975).
Axelrod, J., Wurtman, R. J., Snyder, S. H.: Control of hydroxyindole-O-methyltransferase activity in the rat pineal gland by environmental lighting. J. Biol. Chem. 240, 949–954 (1965).
Axelrod, J., Shein, H. M., Wurtman, R. J.: Stimulation of 14C-melatonin synthesis from 14C-tryptophan by noradrenaline in rat pineal in organ culture. Proc. Natl. Acad. Sci. U.S.A. 62, 544–549 (1969).
Cardinali, D. P., Larin, F., Wurtman, R. J.: Action spectra for effects of light on hydroxyindole-O-methyltransferase in rat pineal, retina and harderian gland. Endocrinology 91, 877–886 (1971).
Cardinali, D. P., Lynch, H. J., Wurtman, R. J.: Binding of melatonin to human and rat plasma proteins. Endocrinology 91, 1213–1218 (1972).
Cheesman, D. W., Fariss, B. L.: Isolation and characterization of a gonadotropin-inhibiting substance from bovine pineal gland. Proc. Soc. Exp. Biol. Med. 133, 1254–1256 (1970).
Fisher, L., Cusack, M. B., Fernstrom, J. D.: Development of a new radioimmunoassay for arginine vasotocin. Neuroscience Abstract 3, 344 (1977).
Hedlund, L., Lischko, M. M., Rollag, M. D., Niswender, G. D.: Melatonin: daily cycle in plasma and cerebrospinal fluid of calves. Science 195, 686–687 (1977).
Hirata, F., Hayaishi, O., Tokuyama, T., Seno, S.: In vitro and in vivo formation of two new metabolites of melatonin. J. Biol. Chem. 249, 1311–1313(1974).
Jimerson, D. C., Lynch, H. J., Post, R. M., Wurtman, R. J., Bunney, W. E.: Urinary melatonin rhythms during sleep deprivation in depressed patients and normals. Life Sci. 20, 1501–1508 (1977).
Klein, D. C., Berg, G. R.: Pineal gland: stimulation of melatonin production by norepinephrine involves cyclic AMP mediated stimulation of N-acetyltransferase. Adv. Biochem. Psychopharmacol. 3, 241–263 (1970).
Klein, D. C., Berg, G. R., Weiler, J., Glinsman, W.: Pineal gland: dibutyryl cyclic adenosine monophosphate stimulation of labeled melatonin production. Science 167, 1738–1740 (1970).
Klein, D. C., Weiler, J. R.: Indole metabolism in the pineal gland: a circadian rhythm in N-acetyltransferase. Science 169, 1093–1095 (1970).
Lynch, H. J., Eng, J. P., Wurtman, R. J.: Control of pineal indole biosynthesis by changes in sympathetic tone caused by factors other than environmental lighting. Proc. Natl. Acad. Sci. U.S.A. 70, 1704–1707 (1973 a).
Lynch, H. J., Wang, P., Wurtman, R. J.: Increase in rat pineal melatonin content following L-dopa administration. Life Sci. 12, 145–151 (1973 b).
Lynch, H. J., Wurtman, R. J., Moskowitz, M. A., Archer, M. C., Ho, M. H.: Daily rhythm in human urinary melatonin. Science 187, 169 (1975 a).
Lynch, H. J., Ozaki, Y., Shakal, D., Wurtman, R. J.: Melatonin excretion of man and rats: effects of time of day, sleep, pinealectomy and food consumption. Int. J. Biometeorol. 19, 267–279 (1975 b).
Lynch, H. J., Ho, M., Wurtman, R. J.: The adrenal medulla may mediate the increase in pineal melatonin synthesis induced by stress, but not that caused by exposure to darkness. J. Neural Transm. 40, 87–97 (1977 a).
Lynch, H. J., Ozaki, Y., Wurtman, R. J.: Unpublished observations (1977 b).
Minneman, K. P., Lynch, H. J., Wurtman, R. J.: Relationship between environmental light intensity and retina-mediated suppression of rat pineal serotonin-N-acetyltransferase. Life Sci. 15, 1791–1796 (1974).
Ozaki, Y., Lynch, H. J.: Presence of melatonin in plasma and urine of pinealectomized rats. Endocrinology 99, 641–644 (1976).
Ozaki, Y., Lynch, H. J., Wurtman, R. J.: Melatonin in rat pineal, plasma, and urine: 24-hour rhythmicity and effect of chlorpromazine. Endocrinology 98, 1418–1424 (1976).
Ozaki, Y., Wurtman, R. J., Alonso, R., Lynch, H. J.: Melatonin secretion decreases during the proestrous stage of the rat estrous cycle. Proc. Natl. Acad. Sci. U.S.A. 75, 531–534 (1977).
Pavel, S., Petrescu, S.: Inhibition of gonadotropin by a highly purified pineal peptide and by synthetic arginine vasotocin. Nature 212, 1054 to 1055 (1966).
Quay, W. B.: Circadian rhythms in rat pineal serotonin and its modification by estrous cycle and photoperiod. Gen. Comp. Endocrinol. 3, 473–479 (1963).
Ralph, C. L., Lynch, H. J.: A quantitative melatonin bioassay. Gen. Comp. Endocrinol. 15, 334–338 (1970).
Ralph, C. L., Mull, D., Lynch, H. J., Hedlund, L.: A melatonin rhythm persists in rat pineals in darkness. Endocrinology 89, 1361–1366 (1971).
Rollag, M. D., Niswender, G. D.: Radioimmunoassay of serum concentrations of melatonin in sheep exposed to different lighting regimens. Endocrinology 98, 482–489 (1976).
Shein, H. M., Wurtman, R. J.: Cyclic adenosine monophosphate: stimulation of melatonin and serotonin synthesis in cultured rat pineals. Science 166, 519–520 (1969).
Shein, H. M., Wurtman, R. J., Axelrod, J.: Synthesis of serotonin by pineal gland of the rat in organ culture. Nature 213, 730–731 (1967).
Smith, I., Mullen, P. E., Silman, R. E., Snedden, W., Wilson, B. W.: Absolute identification of melatonin in human plasma and cerebrospinal fluid. Nature 260, 718–719 (1976).
Wilson, B.: Application of mass spectrometry to study of the pineal gland. Proceedings, International Symposium on the Pineal Gland (Jerusalem, 1977). Wien-New York: Springer. 1978.
Wilson, B. W., Snedden, W., Silman, R. E., Smith, I., Mullen, P.: A gas chromatographic-mass spectrometry method for the quantitative analysis of melatonin in plasma and cerebrospinal fluid. Analyt. Biochem. 81, 283–291 (1977).
Wilson, B., Lynch, H. J., Ozaki, Y.: Paper in preparation.
Wurtman, R. J., Axelrod, J., Phillips, L. S.: Melatonin synthesis in the pineal gland: control by light. Science 142, 1071–1073 (1963).
Wurtman, R. J., Axelrod, J., Kelly, D. E.: The Pineal. New York: Academic Press. 1968 a.
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).
Wurtman, R. J., Shein, H. M., Axelrod, J., Larin, F.: Incorporation of 14C-tryptophan into 14C-protein by cultured rat pineals: stimulation by L-norepinephrine. Proc. Natl. Acad. Sci. U.S.A. 62, 749–755 (1969).
Wurtman, R. J., Shein, H. M., Larin, F.: Mediation by β-adrenergic receptors of effect of norepinephrine on pineal synthesis of 14C-serotonin and 14C-melatonin. J. Neurochem. 18, 1683–1687 (1971).
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Wurtman, R.J., Ozaki, Y. (1978). Physiological Control of Melatonin Synthesis and Secretion: Mechanisms Generating Rhythms in Melatonin, Methoxytryptophol, and Arginine Vasotocin Levels and Effects on the Pineal of Endogenous Catecholamines, the Estrous Cycle, and Environmental Lighting. In: Nir, I., Reiter, R.J., Wurtman, R.J. (eds) The Pineal Gland. Journal of Neural Transmission, vol 13. Springer, Vienna. https://doi.org/10.1007/978-3-7091-4427-5_6
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