Skip to main content
SpringerLink
Log in

The protective effect of melatonin and epithalon on hypothalamic regulation of the reproductive function in female rats in a model of its premature aging and on the estrous cycles of aging animals in different lighting conditions

  • Published:
Advances in Gerontology Aims and scope Submit manuscript

Abstract

Possible neuroprotective effects of melatonin (pineal gland hormone) and epithalon (peptide preparation) on estrous cycles and the central part of the reproductive function regulation in female rats under the influence of unfavorable ecological factors were studied. Estrous cycles of young, mature, and aging rats exposed to light pollution were characterized. The daily dynamics and average daily content of biogenic amines in the hypothalamic areas responsible for gonadoliberin synthesis and secretion were studied in animals of different age groups. The influence of the chemical effect on the noradrenergic system of the medial preoptic area and the dopaminergic system of median eminence with arcuate hypothalamic nuclei was studied in a model of premature aging of the reproductive function. It was established that the introduction of melatonin (pineal gland hormone) and epithalon (peptide preparation) is able to remove a number of the disturbances in the hypothalamic and ovarian parts of the reproductive system observed under conditions of permanent lighting and neurotoxic 1,2-dimethylhydrazine xenobiotic on the experimental animals. The results obtained indicate an important role of the pineal gland in the development of the circadian signal required for realization of the pre-ovulatory peak of gonadoliberin secretion and a protective effect of melatonin and epithalon, which is able to smooth away unfavorable ecological effects on the reproductive function of female rats with normal estrous cycles.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ailamazyan, E.K., Belyaeva, T.V., Vinogradova, E.G., and Shutova, I.A., Reproductive health as the criteria of bioecological assessment of environment, Vestn. Ross. Assots. Akusher.-Ginekol., 1997, no. 3, pp. 72–78.

    Google Scholar 

  2. Anisimov, V.N., Role of epiphysis (pineal glad) in aging), Usp. Gerontol., 1998, vol. 2, no. 2, pp. 74–81.

    Google Scholar 

  3. Anisimov, V.N., Molekulyarnye i fiziologicheskie mekhanizmy stareniya (Molecular and Physiological Mechanisms of Aging), Sankt-Petersburg: Nauka, 2003.

    Google Scholar 

  4. Anisimov, V.N., Arutjunyan, A.V., and Khavinson, V.Kh., Melatonin and epithalamin inhibit lipid peroxidation in rats, Dokl. Ross. Akad. Nauk, 1996, vol. 348, no. 2, pp. 265–267.

    CAS  Google Scholar 

  5. Anisimov, V.N., Khavinson, V.Kh., Zavarzina, N.Yu., et al., Influence of peptide bioregulators and melatonin on parameters of biological age and longevity of mice, Usp. Gerontol., 2000, vol. 4, no. 4, pp. 88–96.

    Google Scholar 

  6. Arutjunyan, A.V., Kozina, L.S., and Arutyunov, V.A., Study of toxic effect of prenatal hyperhomocysteine anemia on a progeny, Zh. Akusher. Zhen. Boleznei, 2010, vol. 59, no. 4, pp. 14–21.

    Google Scholar 

  7. Arutjunyan, A.V., Stepanov, M.G., and Korenevskii, A.V., Disruption of neuromedial link of hypothalamic regulation of reproductive function affected by neurotoxic xenobiotics, Neirokhimiya, 1998, vol. 15, no. 4, pp. 264–270.

    Google Scholar 

  8. Arutjunyan, A.V., Stepanov, M.G., Kerkeshko, G.O., and Ailamazyan, E.K., Disruption of hypothalamic regulation of reproductive function affected by neurotoxic compounds and melatonin, Zh. Akush. Zhen. Boleznei, 2003, vol. 52, no. 2, pp. 77–85.

    Google Scholar 

  9. Arutjunyan, A.V., Kerkeshko, G.O., Anisimov, V.N., et al., Disruption of circadian rhythms of biogenic amines in hypothalamus of the rats after introduction of 1,2-dimethylhydrasine, Vopr. Onkol., 2001, vol. 47, no. 5, pp. 608–615.

    Google Scholar 

  10. Arutjunyan, A.V., Kerkeshko, G.O., Stepanov, M.G., et al., Investigation of mechanism of disruption of hypothalamic regulation of reproductive functions, Zh. Akush. Zhen. Boleznei, 2005, vol. 54, no. 1, pp. 57–63.

    Google Scholar 

  11. Babichev, V.N., Sexual hormones and central nervous system, Ross. Khim. Zh., 2005, vol. 49, no. 1, pp. 94–103.

    CAS  Google Scholar 

  12. Goncharova, N.D., Khavinson, V.Kh., and Lapin, B.A., Pineal’naya zheleza i vozrastnaya patologiya (mekhanizmy i korrektsiya) (Pineal Gland and Age Pathology: Mechanisms and Correction), St. Petersburg: Nauka, 2007.

    Google Scholar 

  13. Kerkeshko, G.O., Stepanov, M.G., Korenevskii, A.V., et al., Influence of melatonin on hypothalamic regulation of reproductive functions in rats at the constant effect of xenobiotics, Neirokhimiya, 2001, vol. 18, no. 1, pp. 84–91.

    Google Scholar 

  14. Kishkun, A.A., Biologicheskii vozrast i starenie: vozmozhnosti opredeleniya i metody korrektsii (The Methods of Determination and Correction of Biological Age and Aging), Moscow: Geotar-Media, 2008.

    Google Scholar 

  15. Korenevskii, A.V., Milyutina, Yu.P., Stepanov, M.G., et al., Relationship between circadian and ovarian cycles in hypothalamic regulation of reproduction, Zh. Akush. Zhen. Boleznei, 2007, vol. 56, no. 4, pp. 24–30.

    Google Scholar 

  16. Morozov, V.G. and Khavinson, V.Kh., Peptidnye bioregulyatory (25-letnii opyt eksperimental’nogo i klinicheskogo izucheniya) (Peptide Bioregulators: 25 Years of Experimental and Clinical Studies), St. Petersburg: Nauka, 1996.

    Google Scholar 

  17. Khavinson, V.Kh., Patent RF 2161501, 2001.

  18. Khavinson, V.Kh. and Anisimov, V.N., Peptidnye bioregulyatory i starenie (Peptide Bioregulators and Aging), St. Petersburg: Nauka, 2003.

    Google Scholar 

  19. Khavinson, V.Kh. and Morozov, V.G., Peptidy epifiza i timusa v regulyatsii stareniya (Importance of Peptides of Epiphysis and Thymus in Aging Regulation), St. Petersburg: Foliant, 2001.

    Google Scholar 

  20. Arutjunyan, A.V., Kerkeshko, G.O., Anisimov, V.N., et al., Disturbances of diurnal rhythms of biogenic amines contents in hypothalamic nuclei as an evidence of neurotropic effects of enterotropic carcinogen 1,2-dimethylhydrazine, Neuroendocrinol. Lett., 2001, vol. 22, no. 4, pp. 229–237.

    PubMed  CAS  Google Scholar 

  21. Chiba, A., Akema, T., and Toyoda, J., Effects of pinealectomy and melatonin on the timing of the proestrous luteinizing hormone surge in the rat, Neuroendocrinology, 1994, vol. 59, no. 2, pp. 163–168.

    Article  PubMed  CAS  Google Scholar 

  22. Diaz, E., Fernandez, C., Castrillon, P.O., et al., Effect of exogenous melatonin on neuroendocrine-reproductive function of middle-aged female rats, J. Reprod. Fertil., 1999, vol. 117, no. 2, pp. 331–337.

    Article  PubMed  CAS  Google Scholar 

  23. Everett, J.W. and Sawyer, C.H., A 24-hour periodicity in the “LH-release apparatus” of female rat, disclosed by barbiturate sedation, Endocrinology, 1950, vol. 47, no. 3, pp. 198–218.

    Article  PubMed  CAS  Google Scholar 

  24. Harney, J.P., Scarbrough, K., Rosewell, K.L., and Wise, P.M., In vivo antisense antagonism of vasoactive intestinal peptide in the suprachiasmatic nuclei causes aging-like changes in the estradiolinduced luteinizing hormone and prolactin surges, Endocrinology, 1996, vol. 137, no. 9, pp. 3696–3701.

    PubMed  CAS  Google Scholar 

  25. Korenevsky, A.V., Milyutina, Yu.P., Stepanov, M.G., et al., Circadian and diurnal rhythms of catecholamines in hypothalamic areas responsible for regulation of reproduction in female rats are disturbed by neurotoxicants and corrected by melatonin, in Circadian Rhythms: Biology, Cognition and Disorders, Golovkin, L. and Maliszkewicz, A., New York: Nova Sci. Publ., 2012, pp. 187–208.

    Google Scholar 

  26. Mohankumar, P.S., Thyagarajan, S., and Quadri, S.K., Correlations of catecholamine release in the medial preotic area with proestrous surges of luteinizing hormone and prolactine: effects of aging, Endocrinology, 1994, vol. 135, no. 1, pp. 119–126.

    PubMed  CAS  Google Scholar 

  27. Palm, I.F., van der Beek, E.M., Wiegant, V.M., et al., Vasopressin induces a luteinizing hormone surge in ovariectomized, estradiol-treated rats with lesions of the suprachiasmatic nucleus, Neuroscience, 1999, vol. 93, no. 2, pp. 659–666.

    Article  PubMed  CAS  Google Scholar 

  28. Palm, I.F., van der Beek, E.M., Wiegant, V.M., et al., The stimulatory effect of vasopressin on the luteinizing hormone surge in ovariectomized, estradiol-treated rats is time-dependent, Brain Res., 2001, vol. 901, nos. 1–2, pp. 109–116.

    Article  PubMed  CAS  Google Scholar 

  29. Pandi-Perumal, S.R., Zisapel, N., Srinivasan, V., and Cardinali, D.P., Melatonin and sleep in aging population, Exp. Gerontol., 2005, vol. 40, no. 12, pp. 911–925.

    Article  PubMed  CAS  Google Scholar 

  30. Pévet, P., Bothorel, B., Slotten, H., and Saboureau, M., The chronobiotic properties of melatonin, Cell Tissue Res., 2002, vol. 309, no. 1, pp. 183–191.

    Article  PubMed  CAS  Google Scholar 

  31. Pierpaoli, W. and Maestroni, G.J., Melatonin: a principal neuroimmunoregulatory and anti-stress hormone: its anti-aging effects, Immunol. Lett., 1987, vol. 16, nos. 3–4, pp. 355–361.

    Article  PubMed  CAS  Google Scholar 

  32. Rasmussen, D.D., Diurnal modulation of rat hypothalamic gonadotropine-releasing hormone release by melatonin in vitro, J. Endocrinol. Invest., 1993, vol. 16, no. 1, pp. 1–7.

    Article  PubMed  CAS  Google Scholar 

  33. Simonneaux, V. and Ribelayga, C., Generation of the melatonin endocrine message in mammals: a review of the complex regulation of melatonin synthesis by norepinephrine, peptides, and other pineal transmitters, Pharmacol. Rev., 2003, vol. 55, no. 2, pp. 325–395.

    Article  PubMed  CAS  Google Scholar 

  34. van der Beek, E.M., Circadian control of reproduction in the female rat, Prog. Brain Res., 1996, vol. 111, pp. 295–320.

    Article  PubMed  Google Scholar 

  35. Wise, P.M., Alterations in the proestrous pattern of median eminence LHRH, serum LH, FSH, estradiol and progesterone concentrations in middle-aged rats, Life Sci., 1982, vol. 12, no. 2, pp. 165–173.

    Article  Google Scholar 

  36. Wise, P.M., Smith, M.J., Dubai, D.B., et al., Neuroendocrine modulation and repercussions of female reproductive aging, Recent Prog. Horm. Res., 2002, vol. 57, pp. 235–256.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Ott Research Institute of Obstetrics and Gynecology, Northwest Branch, Russian Academy of Medical Sciences, Mendeleevskaya liniya 3, St. Petersburg, 199034, Russia

    A. V. Korenevsky, Yu. P. Milyutina & A. V. Arutjunyan

  2. Petrozavodsk State University, pr. Lenina 33, Petrozavodsk, 185910, Russia

    A. V. Bukalyov, Yu. P. Baranova & I. A. Vinogradova

Authors
  1. A. V. Korenevsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu. P. Milyutina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. V. Bukalyov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yu. P. Baranova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. I. A. Vinogradova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. V. Arutjunyan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. V. Arutjunyan.

Additional information

Original Russian Text © A.V. Korenevsky, Yu.P. Milyutina, A.V. Bukalyov, Yu.P. Baranova, I.A. Vinogradova, A.V. Arutjunyan, 2013, published in Uspekhi Gerontologii, 2013, Vol. 26, No. 2, pp. 263–274.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Korenevsky, A.V., Milyutina, Y.P., Bukalyov, A.V. et al. The protective effect of melatonin and epithalon on hypothalamic regulation of the reproductive function in female rats in a model of its premature aging and on the estrous cycles of aging animals in different lighting conditions. Adv Gerontol 4, 67–77 (2014). https://doi.org/10.1134/S2079057014010044

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S2079057014010044

Keywords

Search

Navigation