Experimental Studies of the Pineal Gland Preparation Epithalamin

  • Vladimir Kh. Khavinson
  • V. G. Morozov
  • Vladimir N. Anisimov


Twenty-five years of study have shown a wide spectrum of high biological activity of the pineal peptide preparation epithalamin. Long-term exposure to epithalamin was followed by an increase in the mean and maximum life spans and slower rates of aging of rats, mice, and D. melanogaster. Epithalamin increases pineal synthesis of serotonin, N-acetylserotonin, and melatonin and night pineal secretion of melatonin in adult and old rats. The pineal preparation decreases the luteinizing hormone and prolactin levels in adult male rats as well as the threshold of the hypothalamopituitary complex to feedback inhibition by estrogens in old female rats; it slows dawn age-related cessation of estrous function in rats and induces the recurrence of estrous cydes and fertility in old, persistently estrous rats. Epithalamin increases the levels of triiodothyronine and decreases thyroxine in serum of adult rats. It further decreases the levels of corticosterone in the serum of mice and increases the susceptibility of the hypothalamo-pituitary complex to the homeostatic inhibition of adrenocorticotropic function by glucocorticoids in old rats. Serum insulin and triglyceride levels in rabbits are decreased by epithalamin and the tolerance to glucose and diuresis are increased. With respect to immune function, it was found that T and B cell-mediated immunity in adult and old mice as well as the titer of thymic serum factor and the titer of thymosin-like compounds in old mice are stimulated by the pineal peptide preparation in the same way as the colony-forming activity of splenocytes in pinealectomized rats. Epithalamin inhibits spontaneous and induced carcinogenesis and is a potent antioxidant, decreasing lipid peroxidation and stimulating the activity of CuZn superoxide dismutase. The obtained results demonstrate a high efficiency of epithalamin therapy for prophylaxis of age-related pathology, including cancer, showing a new physiological way to slow down pathological processes and to extend human life spans.


Pineal Gland Luteinizing Hormone Level Maximum Life Span CuZn Superoxide Dismutase Pineal Extract 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Anisimov VN (1987) Pineal gland preparations. In: Anisimov VN (ed) Carcinogenesis and Aging. Vol. 2. CRC Press Inc, Boca Raton, pp 69–72Google Scholar
  2. Anisimov VN (1988) Pineal gland, aging and carcinogenesis. In: Gupta D, Attanasio A, Reiter RJ (eds) The Pineal Gland and Cancer. Brain Research Promotion, London and Tübingen, pp 107–118Google Scholar
  3. Anisimov VN, Dilman VM (1975) Increase of hypothalamic sensitivity to inhibiting effect of estro-gens induced by administration of L-DOPA, diphenylhydantoin, epithalamin and phenformin in old rats. Bull ExpBiol Med 80: 96–98Google Scholar
  4. Anisimov VN, Khavinson VK (1991) Effect of polypeptide pineal preparation on life span and spontaneous tumor incidence in old female rats. Dokl Akad Nauk USSR 319: 250–254Google Scholar
  5. Anisimov VN, Reiter RJ (1990) The function of pineal gland in cancer and aging Vopr Onkol 36: 259–268PubMedGoogle Scholar
  6. Anisimov VN, Khavinson VKh, Morozov VG, Dilman VM (1973 a) The lowering of the threshold of sensitivity of hypothalamo-pituitary system to estrogen action under influence of pineal extract in old female rats. Dokl.Acad.Nauk USSR 213: 483–485Google Scholar
  7. Anisimov VN, Morozov VG, Khavinson VKh, Dilman VM (1973 b) Comparison of anti-tumor activity of pineal and hypothalamus extracts, melatonin and sygetin in mice with transplanted mammary carcinoma. Vopr Onkol 19: 99–101Google Scholar
  8. Anisimov VN, Khavinson VKh, Morozov VG (1982 a) Carcinogenesis and aging IV. Effect of low- molecular factors of thymus, pineal gland and anterior hypothalamus on immunity, tumor incidence and life span of C3H/Sn mice. Mech Ageing Dev 19: 245–258Google Scholar
  9. Anisimov VN, Miretski GI, Morozov VG, Khavinson VKh (1982 b) Effect of polypeptide factors of thymus and epiphysis on radiation carcinogenesis. Bull Exp Biol Med 94: 26–29Google Scholar
  10. Anisimov VN, Morozov VG, Khavinson VKh (1982 c) Increase of life span and decrease of tumor incidence in C3H/Sn mice under influence of polypeptide factors of thymus and pineal gland. Dokl Akad Sei USSR 263: 742–745Google Scholar
  11. Anisimov VN, Morozov VG, Khavinson VKh (1987) Effect of polypeptide factors of thymus, bone marrow, epiphysis and blood vessels on life span and tumor development in mice. Dokl Akad Nauk USSR 293: 1000–1004Google Scholar
  12. Anisimov VN,Loktionov AS, Morozov VG, Khavinson VKh (1988) Increase of life span and decrease of tumor incidence in mice treated with polypeptide factors of thymus and pineal gland in various age. Dokl Akad Nauk USSR 302: 473–476Google Scholar
  13. Anisimov VN, Loktionov AS, Khavinson VKh, Morozov VG (1989) Effect of low-molecular-weight factors of thymus and pineal gland on life span and spontaneous tumour development in female mice of different age. Mech Ageing Dev 49: 245–257PubMedCrossRefGoogle Scholar
  14. Anisimov VN, Bondarenko LA, Khavinson VKh (1990) The pineal peptides: interaction with in-doles and the role in aging and cancer. In: Gupta D, Wollmann HA, Ranke MB (eds) Neuro- endocrinology: New Frontiers. Brain Research Promotion, London and Tübingen, pp 317–325Google Scholar
  15. Anisimov VN, Bondarenko LA, Khavinson VKh (1991) Effect of pineal peptide preparation (epithalamin) on life span and pineal and serum melatonin in rats. In: Abstracts of the 4th Int. Congress of International Association of Biomedical Gerontology, Ancona, June 20–24 1991, p 238Google Scholar
  16. Anisimov VN, Bondarenko LA, Khavinson VKh (1992) Effect of pineal peptide preparation (epi- thalamin) on life span and pineal and serum melatonin level in old rats. Ann NY Acad Sei 673: 53–57CrossRefGoogle Scholar
  17. Anisimov VN, Khavinson VKh, Morozov VG (1994) Twenty years of study on effects of pineal peptide preparation: Epithalamin in experimental gerontology and oncology. Ann NY Acad Sei 719: 483–493CrossRefGoogle Scholar
  18. Anisimov VN, Prokopenko VM, Khavinson VKh (1995) Melatonin and epithalamin inhibit process of free radical oxidation in rats. Dokl Akad Nauk 343: 557–559PubMedGoogle Scholar
  19. Anisimov VN, Arutyunian AV, Khavinson VKh (1996)) Melatonin and epithalamin inhibit process of lipid peroxidation in rats. Dokl Akad Nauk 348: 265–267Google Scholar
  20. Anisimov VN, Mylnikov SV, Oparina TI, Khavinson VKh (1997) Effect of melatonin and pineal peptide preparation epithalamin on life span and free radical oxidation in Drosophila melano- gaster. Mech Ageing Dev 91: 81–91CrossRefGoogle Scholar
  21. Armstrong SM, Redman JR (1991) Melatonin: a chronobiotic with anti-aging properties? Med Hypotheses 34: 300–309PubMedCrossRefGoogle Scholar
  22. Arushanian EB, Baturin VA, Ovanesov KB (1990) Chronic administration of pineal peptides change the circadian locomotor activity and time-course of forced swimming in rats. J Pineal Res 9: 271–277PubMedCrossRefGoogle Scholar
  23. Aubert C, Janiaud P, Lecalvez J (1980) Effect of pinealectomy and melatonin on mammary tumor growth in Sprague-Dawley rats under different conditions of ligthing. J Neural Transm 47: 121–130PubMedCrossRefGoogle Scholar
  24. Bartsch H, Bartsch C (1988) Unidentified pineal substances with anti-tumor activity. In: Gupta D, Attanasio A, Reiter RJ (eds) The Pineal Gland and Cancer. Brain Res Promotion, London and Tübingen, pp 369–376Google Scholar
  25. Bartsch C, Bartsch H, Lippert TH (1992 a) The pineal gland and cancer: facts, hypotheses and per¬spectives. The Cancer J 5: 194–199Google Scholar
  26. Bartsch H, Bartsch C, Simon WE, Flehmig B, Ebels I, Lippert TH (1992 b) Antitumor activity of the pineal gland: effect of unidentified substances versus the effect of melatonin. Oncology 49: 27–30Google Scholar
  27. Belokrylov GA, Morozov VG, Khavinson VKh, Sofronov BN (1976) Effect of low-molecular extracts from heterologous thymus, epiphysis and hypothalamus on the immune response of mice. Bull Exp Biol Med 81: 202–204Google Scholar
  28. Belozertsev YA, Tertyshnik ID, Spinko AA, Grudinin AN (1987) Restoration by pineal cytomedins of learning and homeostatic disturbances. In: Abstracts of Scientific Conference “The Role of Peptide Bioregulators (Cytomedins) in Regulation of Homeostasis”. Yakovlev GM (ed) Military Medical Academy Publ, Leningrad, pp 13–14Google Scholar
  29. Benson B (1977) Current status of pineal peptides. Neuroendocrinology 24: 241–248PubMedCrossRefGoogle Scholar
  30. Blask DE (1990) The emerging role of the pineal gland and melatonin in oncogenesis. In: Wilson BW, Stevens RG, Anderson LE (eds) Extremely Low Frequency Electromagnetic Fields: the Question of Cancer. Battelle Press, Columbus, pp 319–335Google Scholar
  31. Blask DE, Vaughan MK, Reiter RJ (1983) Pineal peptides and reproduction. In: Relkin R (ed) The Pineal Gland. Elsevier, Amsterdam, pp 201–224Google Scholar
  32. Bondarenko LA, Anisimov VN (1990) Effect of polypeptide pineal preparation epithalamin on serotonin metabolism in the pineal gland of rats. Bull Exp Biol Med 110: 150–151Google Scholar
  33. Bondarenko LA, Anisimov VN (1992) Age-related peculiarities of effect of epithalamin on metabolism of serotonin in pineal gland of rats. Bull Exp Biol Med 113: 194–195Google Scholar
  34. Bondarenko LA, Lukashova OP, Rom-Boguslavkaya ES (1992) Chronopharmacological aspects of the effect of pineal bioregulator epithalamin on morpho-functional activity of pineal gland. In: Yakovlev GM (ed) Abstracts of the Symposium “Peptide Bioregulators–Cytomedins” Medical Military Academy Publ, St.Petersburg, pp 34–35Google Scholar
  35. Dilman VM, Anisimov VN (1979) Hypothalamic mechanisms of ageing and of specific age pathology - I. Sensitivity threshold of hypothalamo-pituitary complex to homeostatic stimuli in the reproductive system. Exp Gerontol 14: 161–174PubMedCrossRefGoogle Scholar
  36. Dilman VM, Anisimov VN, Ostroumova MN, Khavinson VKh, Morozov VG (1979 a) Increase in lifespan of rats following polypeptide pineal extract treatment. Exp Pathol 17: 539–545Google Scholar
  37. Dilman VM, Anisimov VN, Ostroumova MN, Khavinson VKh, Morozov VG, Azarova MA (1979b) Study of the anti-tumor effect of polypeptide pineal extract. Oncology 36: 274–280PubMedCrossRefGoogle Scholar
  38. Gadzhieva TS, Blinova TS (1980) Effect of epithalamin on gonadotropic function of pituitary and on ovaries. Akush Gynekol 9: 15–18Google Scholar
  39. Grinevich YuA, Bendyug GD, Bobrov LI, Labunets IF, Kireeva ES (1992) Effect of polypeptide factors of thymus and pineal gland on spontaneous development of lymphomas in AKR mice. In: Yakovlev GM (ed) Abstracts of the Symposium “Peptide Bioregulators–Cytomedines”. Medical Military Academy Publ, St.Petersburg, pp 47–48Google Scholar
  40. Gupta D, Haldar C, Coeleveld M, Roth J (1993) Ontogeny, circadian rhythm pattern, and hormonal modulation of 5-alpha-dihydrotestosterone receptors in the rat pineal. Neuroendocrinology 57: 45–53PubMedCrossRefGoogle Scholar
  41. Karpov RS, Slepushkin VD, Mordovin VF, Khavinson VKh, Morozov VG, Grischenko VI (1985) The Use of Pineal Preparations in Clinical Practice. Tomsk Univ Publ, TomskGoogle Scholar
  42. Khavinson VKh, Morozov VG (1992) The Preparations of Epiphysis and Thymus in Gerontology. Institute of Bioregulation and Gerontology Publ, St. PetersburgGoogle Scholar
  43. Khavinson V.Kh, Morozov VG, Grintzevich II, Knorre ZD (1977) Influence of polypeptide extracted from the anterior hypothalamus and the epiphysis on the cells of the hypothalamo-hypophyseal neurosecretory system. Arch Anat Histol Embryol 73: 100–104Google Scholar
  44. Labunets IF (1992) Effect of epithalamin on immune system of young and aged animals. In: Yakovlev GM (ed) Abstracts of the Symposium “Peptide Bioregulators–Cytomedins”, Medical Military Academy Publ, St. Petersburg, pp 85–86Google Scholar
  45. Lapin V, Ebels I (1976) Effect of some low molecular weight sheep pineal fractions and melatonin on different tumours in rats and mice. Oncology 33: 11–13CrossRefGoogle Scholar
  46. Maestroni GJM, Conti A, Pierpaoli W (1987) The pineal gland and the circadian, opiatergic, immune-regulatory role of melatonin. Ann NY Acad Sei 496: 67–77CrossRefGoogle Scholar
  47. Maestroni GJM, Conti A, Pierpaoli W (1989) Melatonin, stress and the immune system. Pineal Res Rev 7: 203–226Google Scholar
  48. Malm OJ, Skaug OE, Lingjaerde P (1959) The effect of pinealectomy on bodily growth, survival rate and 32P uptake in the rat. Acta Endocrinol 30: 22–28PubMedGoogle Scholar
  49. Meites J (1988) Neuroendocrine basis of aging in the rat. In: Everitt AV, Walton JR (eds) Regulation of Neuroendocrine Aging (Interdisciplinary Topics in Gerontology, Vol. 24 ), Karger, Basel, pp 37–50Google Scholar
  50. Morozov VG, Khavinson VKh (1971) The influence of extracts from hypothalamus and pineal gland on some host functions. Proc of the Conference of the Medical Military Academy, Leningrad, pp 127–128Google Scholar
  51. Morozov VG, Khavinson VKh (1974) Effect of pineal extract on the development of experimental tumors and leukemias. Exp Khirurgia 1: 34–38Google Scholar
  52. Morozov VG, Khavinson VKh (1996) Peptide Bioregulators (25-years Experience of Experimental and Clinical Study). Nauka, St.Petersburg.Google Scholar
  53. Noteborn HPJM, Bartsch H, Bartsch C, Mans DRA, Weusten JJAM, Flehmig B, Ebels I, Salemnik CA (1988) Partial purification of a low molecular weight ovine pineal compound(s) with an inhibiting effect on the growth of human melanoma cells in vitro. J Neural Transm 73: 135–155PubMedCrossRefGoogle Scholar
  54. Ostroumova MN, Vasilyeva IA (1976) Effect of pineal extract on the regulation of fat-carbohydrate metabolism. Probl Endocrinol 22: 66–69Google Scholar
  55. Ostroumova MN, Anisimov VN, Syromyatnikov AA, Dilman VM (1976) Decrease of antigonado- tropic factor excretion in patients with cancer of cervix uteri and prostate. Antitumor effect of pineal extract in the experiment. Vopr Onkol 22: 39–43PubMedGoogle Scholar
  56. Parhon CI (1955) Biologia Virstelor - cercetari clinici si experimentali. Acad R.P.R, Bucharest Pierpaoli W (1991) The pineal gland: a circadian or seasonal aging clock? Aging 3: 99–101Google Scholar
  57. Pierpaoli W, Dall’Ara A, Pedrini E, Regelson W (1991) The pineal control of aging: the effects of melatonin and pineal grafting on the survival of older mice. Ann NY Acad Sei 621: 291–313CrossRefGoogle Scholar
  58. Poeggeler B, Reiter RJ, Tan D-X, Chen L-D, Manchester LC (1993) Melatonin, hydroxyl radical-mediated oxidative damage, and aging: a hypothesis. J Pineal Res 14: 151–168PubMedCrossRefGoogle Scholar
  59. Prokopenko NP, Tigranyan RA, Muratovam GL, Plokhoy VI, Khavinson VKh (1989) Properties of the acid extract fraction from epiphysis. Vopr Med Khimii 4: 79–81Google Scholar
  60. Reiter RJ (1981) The mammalian pineal gland: structure and function. Amer J Anat 162: 287–313PubMedCrossRefGoogle Scholar
  61. Reiter RJ (1988) Neuroendocrinology of melatonin. In: Miles A, Philbrick DRS, Tompson C (eds) Melatonin - Clinical Perspectives. Oxford University Press, Oxford, pp 1–42Google Scholar
  62. Riegle GD, Miller AE (1978) Aging effects on the hypothalamic-hypophyseal-gonadal control system in the rat. In: Schneider EL (ed) The Aging Reproductive System (Aging, Vol. 4 ), Raven Press, New York, pp 159–192Google Scholar
  63. Slepushkin VD, Pashinski VG (1982) The Epiphysis and Adaptation of Organism. Tomsk University Publ, TomskGoogle Scholar
  64. Slepushkin VD, Anisimov VN, Khavinson VKh, Morozov VG, Vasiliev NV, Kosykh VA (1990) The Pineal Gland, Immunity and Cancer ( Theoretical and Clinical Aspects ), Tomsk University Publ TomskGoogle Scholar
  65. Trentini GP, De Gaetani C, Criscuolo M (1991) Pineal gland and aging. Aging 3: 103–116PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2001

Authors and Affiliations

  • Vladimir Kh. Khavinson
  • V. G. Morozov
  • Vladimir N. Anisimov

There are no affiliations available

Personalised recommendations