Abstract
In this paper, we investigated the dynamics of aging of the estrous function of female rats kept in the conditions of standard vivarium lighting that received luzindolee—a blocker of melatonin receptors. Every three months, daily, for two weeks, vaginal smears were taken from the animals and a cytological examination of the vaginal contents was conducted. Despite the difference in the mechanisms of the development of melatonin system failure (a decreased production of melatonin and a blockade of melatonin receptors), the effects of the influence on the ovulatory function are similar. With a blockade of melatonin receptors, an appearance of premature signs of aging of the reproductive function in rats was observed. It was manifested by an increased duration of the ovulatory cycle; a decrease in the number of regular cycles; the emergence of irregular cycles; a decrease in the number of short estrous cycles and an increase of long cycles; and the early development of persistent estrus.
Similar content being viewed by others
References
Anisimov, V.N., Molekulyarnye i fiziologicheskie mekhanizmy stareniya (Molecular and Physiological Mechanisms of Aging), St. Petersburg: Nauka, 2008, vol. 1.
Anisimov, V.N., Ailamazyan, E.K., and Baturin, D.A., Light regime,anovulation,and the risk of malignant neoplasms of the female reproductive system: relation mechanisms and prevention, Zh. Akush. Zhen. Bolezn., 2003, vol. 52, no. 2, pp. 47–57.
Anisimov, V.N., Baturin, D.A., and Ailamazyan, E.K., Epiphysis, light, and breast cancer, Vopr. Onkol., 2002, vol. 48, nos. 4–5, pp. 524–535.
Baturin, D.A., Alimova, I.N., Popovich, I.G., et al., Effect of light deprivation on homeostasis, life expectancy, and spontaneous tumor development in HER-2/neu transgenic mice, Vopr. Onkol., 2004, vol. 50, no. 3, pp. 332–338.
Bespyatnykh, A.Yu., Brodskii, V.Ya., Burlakova, O.V., et al., Melatonin: teoriya i praktika (Melatonin: Theory and Practice), Moscow: Medpraktika, 2009.
Vinogradova, I.A., Bukalev, A.V., Zabezhinskii, M.A., et al., Influence of light regime and melatonin on the homeostasis,life time,and development of spontaneous tumors in female rats, Usp. Gerontol., 2007, vol. 20, no. 4, pp. 40–47.
Vinogradova, I.A. and Chernova, I.V., Influence of light regime on age dynamics of estrous function and prolactin level in rat blood serum, Usp. Gerontol., 2006, no. 19, pp. 60–65.
Vinogradova, I.A. and Chernova, I.V., Light regimes and ovulatory function of rats in ontogenesis, Ross. Fiziol. Zh. im. I.M. Sechenova, 2007, vol. 93, no. 1, pp. 90–98.
Gaidin, I.V., Baranova, Yu.P., and Vinogradova, I.A., Influence of day length in Karelia on the estrous function in female rats, Uch. Zap. Petrozavod. Gos. Univ., 2011, no. 6 (119), pp. 45–49.
Di’lman, V.M., Chetyre modeli meditsiny (Four Models of Medicine), Leningrad: Nauka, 1987.
Zaitsev, V.M., Liflyandskii, V.G., and Marinkin, V.I., Prikladnaya meditsinskaya statistika (Applied Medical Statistic Data Analysis), St. Petersburg: Foliant, 2006.
Kabak, Ya.M., Praktikum po andokrinologii. Osnovnye metodiki eksperimental’no-endokrinologicheskikh issledovanii (Practical Manual on Endocrinology: Main Experimental Endocrinological Methods), Moscow: Mosk. Gos. Univ., 1968.
Klochkov, D.V. and Belyaev, D.K., The effect of constant illumination on the reproductive function of rats, Ontogenez, 1977, vol. 8, no. 5, pp. 487–496.
Melatonin: perspektivy primeneniya v klinike (Prospective Implementation of Melatonin in Clinical Practice), Rapoport, S.I., Ed., Moscow: IMA-Press, 2012.
Rukovodstvo po laboratornym zhivotnym i al’ternativnym modelyam v biomeditsinskikh issledovaniyakh (Manual for Laboratory Animals and Alternative Models in Biomedical Studies), Karkishchenko, N.N. and Grachev, S.V., Eds., Moscow: Profil’, 2010.
Eticheskaya ekspertiza biomeditsinskikh issledovanii. Prakticheskie rekomendatsii (Ethical Expertise of Biomedical Studies: Practical Recommendations), Belousov, Yu.B., Ed., Moscow: Ross. O-vo Klin. Issled., 2005.
Beyer, C.E., Steketee, J.D., and Saphier, D., Antioxidant properties of melatonin—an emerging mystery, Biochem. Pharmacol., 1998, vol. 56, pp. 1265–1272.
Brzozowska, I., Ptak-Belowska, A., Pawlik, M., et al., Mucosal strengthening activity of central and peripheral melatonin in the mechanism of gastric defense, J. Physiol. Pharmacol., 2009, vol. 60, suppl. 7, pp. 47–56.
Drazen, D.L., Bilu, D., Bilbo, S.D., et al., Melatonin enhancement of splenocyte proliferation is attenuated by luzindole, a melatonin receptor antagonist, Am. J. Physiol. Regul., Integr. Comp. Physiol., 2001, vol. 280, no. 5, pp. 1476–1482.
Drobnik, J., Owczarek, K., Piera, L., et al., Melatonininduced augmentation of collagen deposition in cultures of fibroblasts and myofibroblasts is blocked by luzindole—a melatonin membrane receptors inhibitor, Pharmcol. Rep., 2013, vol. 65, no. 3, pp. 642–649.
Dubocovich, M.L, Yun, K., Al-Ghoul, W.M., et al., Selective MT2 melatonin receptor antagonists block melatonin-mediated phase advances of circadian rhythms, FASEB J., 1998, vol. 12, no. 12, pp. 1211–1220.
Juszczak, M., Roszczyk, M., Kowalczyk, E., and Stempniak, B., The influence of melatonin receptors antagonists, luzindole and 4-phenyl-2-propionamidotetralin (4-P-P-PDOT),on melatonindependent vasopressin and adrenocorticotropic hormone (ACTH) release from the rat hypothalamo-hypophysial system, J. Physiol. Pharmacol., 2014, vol. 65, no. 6, pp. 777–784.
Negrev, N., Nyagolov, Yu., Zarkova, A., et al., Effects of melatonin and luzindole on plasma levels of tissue factor,tissue factor pathway inhibitor and von Willebrand factor in rats, Scr. Sci. Med., 2015, vol. 47, no. 1, pp. 64–69.
Prata Lima, M.F., Baracat, E.C., and Simones, M.J., Effects of melatonin on the ovarian response to pinealectomy or continuous light in female rats: similarity with polycystic ovary syndrome, Braz. J. Med. Biol. Res., 2004, vol. 37, pp. 987–995.
Shieh, J.M., Wu, H.T., and Cheng, K.C., Melatonin ameliorates high fat diet-induced diabetes and stimulates glycogen synthesis via a PKCzeta-Akt-Gsk3-beta pathway in hepatic cells, J. Pineal Res., 2009, vol. 47, pp. 339–344.
Soares, J.M., Masana, M.I., Ersahin, C., and Dubocovich, M.L., Functional melatonin receptors in rat ovaries at various stages of the estrous cycle, J. Pharmacol. Exp. Ther., 2003, vol. 306, no. 2, pp. 694–702.
Winczyk, K., Fuss-Chmielewska, J., Pawlikowski, M., et al., Luzindole but not 4-phenyl-2-propionamidotetralin (4P-PDOT) diminishes the inhibitory effect of melatonin on murine Colon 38 cancer growth in vitro, Neuroendocr. Lett., 2009, vol. 30, pp. 657–662.
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © O.V. Zhukova, E.S. Obukhova, E.A. Khizhkin, V.A. Ilukha, I.A. Vinogradova, 2016, published in Uspekhi Gerontologii, 2016, Vol. 29, No. 2, pp. 279–285.
Rights and permissions
About this article
Cite this article
Zhukova, O.V., Obukhova, E.S., Khizhkin, E.A. et al. Luzindole accelerates the aging of estrous function of female rats. Adv Gerontol 6, 322–327 (2016). https://doi.org/10.1134/S2079057016040159
Published:
Issue Date:
DOI: https://doi.org/10.1134/S2079057016040159