Pinealectomy and Melatonin Administration in Rats: Their Effects on Plasma Leptin Levels and Relationship with Zinc


The aim of this study was to examine effects of pinealectomy and melatonin administration plasma leptin levels and its relationship with zinc in rats. The study was conducted on 40 adult male Sprague-Dawley rats. They were divided into four groups each containing 10 animals. Group 1 served as control. Group 2 was pinealectomized group. Animals in Group 3 were pinealectomized and injected with melatonin (3 mg/kg/day, ip). Group 4 received melatonin alone (3 mg/kg/day, ip). At the end of the experiments, all animals were decapitated and trunk blood collected. Plasma leptin and zinc levels were determined by radioimmunoassay and Atomic Absorption Spectrophotometer methods, respectively. Although mean weights of the animals at the beginning were not significantly different among the groups, the mean weight of the pinealectomized group was found to be significantly lower than all other groups at the end of a six-month period (p < 0.01). Plasma leptin and zinc levels were the highest in mela-tonin-administered group (group 4; p < 0.01). The lowest plasma leptin and zinc levels were obtained in the pinealectomized group (group 2; p < 0.01). Changes in these two parameters were not statistically significant in groups 1 and 3. Our findings indicate that pinealectomy results in a decrease in leptin and zinc levels in rats, and that melatonin administration to pinealectomized rats prevents the decrease in the these parameters. In addition, long-term administration of melatonin to rats leads to an increase in both leptin and zinc concentrations.


  1. 1.

    Alonso-Vale, M. I., Anhe, G. F., Borges-Silva, C. N., Andreotti, S., Peres, S. B., Cipolla-Neto, J., Lima, F. B. (2004) Pinealectomy alters adipose tissue adaptability to fasting in rats. Metabolism 53, 500–506.

    CAS  PubMed  Google Scholar 

  2. 2.

    Bado, A., Levasseur, S., Attoub, S., Kermorgant, S., Laigneau, J. P., Bortoluzzi, M. N., Moizo, L., Lehy, T., Guerre-Millo, M., Le Marchand-Brustel, Y., Lewin, M. J. (1998) The stomach is a source of leptin. Nature 394, 790–793.

    CAS  PubMed  Google Scholar 

  3. 3.

    Baltaci, A. K., Mogulkoc, R., Bediz, C. S., Kul, A., Ugur, A. (2003) Pinealectomy and zinc deficiency have opposite effects on thyroid hormones in rats. Endocr. Res. 29, 473–481.

    PubMed  Google Scholar 

  4. 4.

    Baltaci, A. K., Mogulkoc, R., Kul, A., Bediz, C. S., Ugur, A. (2004) Opposite effects of zinc and melatonin on thyroid hormones in rats. Toxicology 195, 69–75.

    CAS  PubMed  Google Scholar 

  5. 5.

    Baydas, G., Gursu, F., Canpolat, S., Konar, V., Yasar, A., Canatan, H., Kelestimur, H. (2001) Effects of pinealectomy on the circadian release pattern of leptin in male rat. Neuroendocrinol. Lett. 22, 449–452.

    CAS  PubMed  Google Scholar 

  6. 6.

    Bediz, C. S., Baltaci, A. K., Mogulkoc, R. (2003) Both zinc deficiency and supplementation affect plasma melatonin levels in rats. Acta. Physiol. Hung. 90, 353–359.

    Google Scholar 

  7. 7.

    Bribiescas, R. G. (2003) Effects of oral zinc supplementation on serum leptin levels in ache males of eastern Paraguay. Am. J. Hum. Biol. 15, 681–687.

    PubMed  Google Scholar 

  8. 8.

    Canpolat, S., Sandal, S., Yilmaz, B., Yasar, A., Kutlu, S., Baydas, G., Kelestimur, H. (2001) Effects of pinealectomy and exogenous melatonin on serum leptin levels in male rat. Eur. J. Pharmacol. 428, 145–148.

    CAS  PubMed  Google Scholar 

  9. 9.

    Chehab, F., Lim, M., Lu, R. (1996) Correction of sterility defect in homozygous obese female mice treated with human recombinant leptin. Nat. Genet. 12, 318–320.

    CAS  PubMed  Google Scholar 

  10. 10.

    Chen, M. D., Lin, P. Y. (2000) Zinc-induced hyperleptinemia relates to the amelioration of sucrose-induced obesity with zinc repletion. Obes. Res. 8, 525–529.

    CAS  PubMed  Google Scholar 

  11. 11.

    Chen, M. D., Song, Y. M., Lin, P. Y. (2000) Zinc may be a mediator of leptin production in humans. Life Sci. 66, 214–219.

    Google Scholar 

  12. 12.

    Collins, S., Kuhn, C. M., Petro, A. E., Swick, A. G., Chrunyk, B. A., Surwit, R. S. (1996) Role of leptin in fat regulation. Nature 380, 677.

    CAS  Google Scholar 

  13. 13.

    Considine, R. V., Sinha, M. K., Heiman, M. L., Kriauciunas, A., Stephens, T. W., Nyce, M. R., Ohannesian, J. P., Marco, C. C., McKee, L. J., Bauer, T. L., José, F., Caro, J. F. (1996) Serum immunoreactive-Leptin concentrations in normal-weight and obese humans. N. Engl. J. Med. 334, 292–295.

    CAS  PubMed  Google Scholar 

  14. 14.

    Emilsson, V., Liu, Y. L., Cawthorne, M. A., Morton, N. M., Davenport, M. (1997) Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion. Diabetes 46, 313–316.

    CAS  PubMed  Google Scholar 

  15. 15.

    Fraker, P. J., Jardieu, P., Cook, J. (1987) Zinc deficiency and immune function. Arch. Dermatol. 123, 1699–1701.

    CAS  PubMed  Google Scholar 

  16. 16.

    Gainsford, T., Wilson, T. A., Metcalf, D., Handman, E., McFarlane, C., Ng, A., Nicola, N. A., Alexander, W. S., Hilton, D. J. (1996) Leptin can induce proliferation, differentiation and functional activation of hemopoietic cells. Proc. Natl. Acad Sci. U.S.A. 93, 14564–14568.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Jahnke, G., Marr, M., Myers, C., Wilson, R., Travlos, G., Price, C. (1999) Maternal and developmental toxicity evaluation of melatonin administered orally to pregnant Sprague-Dawley rats. Toxicol. Sci. 50, 271–279.

    CAS  PubMed  Google Scholar 

  18. 18.

    Johnson, S. (2001) Micronutrient accumulation and depletion in schizophrenia, epilepsy, autism and Parkinson’s disease? Med. Hypotheses 56, 641–645.

    CAS  PubMed  Google Scholar 

  19. 19.

    Kamohara, S., Burcelin, R., Halas, J. L., Friedman, J. M., Charron, M. J. (1997) Acute stimulation of glucose metabolism in mice by leptin treatment. Nature 389, 374–377.

    CAS  PubMed  Google Scholar 

  20. 20.

    Kuszak, J., Rodin, M. (1977) A new technique of pinealectomy for adult rats. Experientia 33, 283–284.

    CAS  PubMed  Google Scholar 

  21. 21.

    Lord, G. M., Matarese, G., Howard, J. K., Baker, R. J., Bloom, S. R., Lechler, R. I. (1998) Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394, 897–901.

    CAS  PubMed  Google Scholar 

  22. 22.

    Mangian, H. F., Lee, R. G., Paul, G. L., Emmert, J. L., Shay, N. F. (1998) Zinc deficiency suppresses plasma leptin concentrations in rats. J. Nutr. Biochem. 9, 47–51.

    CAS  Google Scholar 

  23. 23.

    Mantzoros, C. S., Flier, J. S., Rogol, A. D. (1997) A longitudinal assessment of hormonal and physical alterations during normal puberty in boys: rising leptin levels may signal the onset of puberty. J. Clin. Endocrinol. Metab. 82, 1065–1070.

    Google Scholar 

  24. 24.

    Mastronardi, C. A., Walczewska, A., Yu, W. H., Karanth, S., Parlow, A. F., McCann, S. M. (2000) The possible role of prolactin in the circadian rhythm of leptin secretion in male rats. Proc. Soc. Exp. Biol. Med. 224, 152–158.

    CAS  PubMed  Google Scholar 

  25. 25.

    Matkovic, V., Ilich, J. Z., Skugor, M., Badenhop, N. E., Goel, P., Clairmont, A., Klisovic, D., Nahhas, R. W., Landoll, J. D. (1997) Leptin is inversely related to age at menarche in human females. J. Clin. Endocrinol. Metab. 82, 3239–3245.

    CAS  PubMed  Google Scholar 

  26. 26.

    Meguid, M. M., Fetissov, S. O., Varma, M., Sato, T., Zhang, L., Laviano, A., Rossi-Fanelli, F. F. (2000) Hypothalamic dopamine and serotonin in the regulation of food intake. Nutrition 16, 843–857.

    CAS  PubMed  Google Scholar 

  27. 27.

    Mercer, J. G., Moar, K. M., Rayner, D. V., Trayhurn, P., Hoggard, N. (1997) Regulation of Leptin receptor and NPY gene expression in hypothalamus of Leptin-treated obese (ob/ob) and cold exposed lean mice. FEBS Letters 402, 185–188.

    CAS  PubMed  Google Scholar 

  28. 28.

    Mocchegiani, E., Bulian, D., Santarelli, L., Tibaldi, A., Muzzioli, M., Pierpaoli, W., Fabris, N. (1994) The immuno-reconstituting effect of melatonin or pineal grafting and its relation to zinc pool in aging mice. J. Neuroimmunol. 53, 189–201.

    CAS  PubMed  Google Scholar 

  29. 29.

    Mocchegiani, E., Bulian, D., Santarelli, L., Tibaldi, A., Muzzioli, M., Lesnikov, V., Pierpaoli, W., Fabris, N. (1996). The zinc pool is involved in the immune-reconstituting effect of melatonin in pinealectomized mice. J. Pharmacol. Exp. Ther. 277, 1200–1208.

    CAS  PubMed  Google Scholar 

  30. 30.

    Mocchegiani, E., Santarelli, L., Tibaldi, A., Muzzioli, M., Bulian, D., Cipriano, K., Olivieri, F., Fabris, N. (1998) Presence of links between zinc and melatonin during the circadian cycle in old mice: effects on thymic endocrine activity and on the survival. J. Neuroimmunol. 86, 111–122.

    CAS  PubMed  Google Scholar 

  31. 31.

    Mocchegiani, E., Perisin, L., Santarelli, L., Tibaldi, A., Zorzet, S., Rapozzi, V., Giacconi, R., Bulian, D., Giraldi, T. (1999) Melatonin administration in tumor-bearing mice (intact and pinealectomized) in relation to stress, zinc, thymulin and IL-2. Int. J. Immunopharmacol. 21, 27–46.

    CAS  PubMed  Google Scholar 

  32. 32.

    Mustonen, A. M., Nieminen, P., Hyvarinen, H. (2001) Preliminary evidence that pharmacologic melatonin treatment decreases rat ghrelin levels. Endocrine 16, 43–46.

    CAS  PubMed  Google Scholar 

  33. 33.

    Mustonen, A. M., Nieminen, P., Hyvarinen, H., Asikainen, J. (2001) Exogenous melatonin elevates the plasma leptin and thyroxine concentrations of the mink (Mustela vison). Z. Naturforsch. [C] 55, 806–813.

    Google Scholar 

  34. 34.

    Olusi, S., Al-Awadhi, A., Agabeyaka, C., Abraham, M., George, S. (2003) Serum copper levels and not zinc are positively associated with serum leptin concentrations in the healthy adult population. Biol. Trace. Elem. Res. 91, 137–144.

    CAS  PubMed  Google Scholar 

  35. 35.

    Ott, E. S., Shay, N. F. (2001) Zinc deficiency reduces leptin gene expression and leptin secretion in rat adipocytes. Exp. Biol. Med. (Maywood) 226, 841–846.

    CAS  Google Scholar 

  36. 36.

    Pelleymounter, M. A., Cullen, M. J., Baker, M. B., Hecht, R., Winters, D., Bone, T., Collins, F. (1995) Effects of the obese gene-product on body weight regulation in ob/ob mice. Science 269, 540–543.

    CAS  PubMed  Google Scholar 

  37. 37.

    Prasad, A. S. (1985) Clinical manifestations of zinc deficiency. Annu. Rev. Nutr. 5, 341–363.

    CAS  PubMed  Google Scholar 

  38. 38.

    Prunet-Marcassus, B., Desbazeille, M., Bros, A., Louche, K., Delagrange, P., Renard, P., Casteilla, L., Penicaud, L. (2003) Melatonin reduces body weight gain in Sprague-Dawley rats with diet-induced obesity. Endocrinology 144, 5347–5352.

    CAS  PubMed  Google Scholar 

  39. 39.

    Rasmussen, D. D., Boldt, B. M., Wilkinson, C. W., Yellon, S. M., Matsumoto, A. M. (1999) Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels. Endocrinology 140, 1009–1012.

    CAS  PubMed  Google Scholar 

  40. 40.

    Rasmussen, D. D., Mitton, D. R., Larsen, S. A., Yellon, S. M. (2001) Aging-dependent changes in the effect of daily melatonin supplementation on rat metabolic and behavioral responses. J. Pineal. Res. 31, 89–94.

    CAS  PubMed  Google Scholar 

  41. 41.

    Reiter, R. J. (1993) The melatonin rhythm: both a clock and a calendar. Experientia 49, 654–664.

    CAS  PubMed  Google Scholar 

  42. 42.

    Reiter, R. J., Tan, D., Kim, S. J., Manchester, L. C., Qi, W., Garcia, J. J., Cabrera, J. C., El-Sokkary, G., Rouvier-Garay, V. (1999) Augmentation of indices of oxidative damage in life-long melatonin-deficient rats. Mech. Ageing Dev. 110, 157–173.

    CAS  PubMed  Google Scholar 

  43. 43.

    Safai-Kutti, S., Kutti, J. (1986) Zinc supplementation in anorexia nervosa. Am. J. Clin. Nutr. 44, 581–582.

    CAS  PubMed  Google Scholar 

  44. 44.

    Selvais, P. L., Labuche, C., Nguyen, X. N., Ketelslegers, J. M., Denef, J. F., Maiter, D. M. (1997) Cyclic feeding behaviour and changes in hypothalamic galanin and neuropeptide Y gene expression induced by zinc deficiency in the rat. J. Neuroendocrinol. 9, 55–62.

    CAS  PubMed  Google Scholar 

  45. 45.

    Sierra-Honigmann, M. R., Nath, A. K., Murakami, C., Garcia-Cardena, G., Papapetropoulos, A., Sessa, W. C., Madge, L. A., Schechner, J. S., Schwabb, M. B., Polverini, P. J., Flores-Riveros, J. R. (1998) Biological action of leptin as an angiogenic factor. Science 281, 1683–1686.

    CAS  PubMed  Google Scholar 

  46. 46.

    Skwarlo-Sonta, K. (1996) Functional connections between the pineal gland and immune system. Acta Neurobiol. Exp. (Wars.) 56, 341–357.

    CAS  Google Scholar 

  47. 47.

    Tallman, D. L., Taylor, C. G. (2003) Effects of dietary fat and zinc on adiposity, serum leptin and adipose fatty acid composition in C57BL/6J mice. J. Nutr. Biochem. 14, 17–23.

    CAS  PubMed  Google Scholar 

  48. 48.

    Trayhurn, P., Hoggard, N., Mercer, J. G., Rayner, D. V. (1999) Leptin: fundamentel aspects. Int. J. Obes. Relat. Metab. Disord. 23, 22–28.

    CAS  PubMed  Google Scholar 

  49. 49.

    Wada, L., King, J. C. (1986) Effect of low zinc intakes on basal metabolic rate, thyroid hormones and protein utilization in adult men. J. Nutr. 116, 1045–1053.

    CAS  PubMed  Google Scholar 

  50. 50.

    Wilkinson, M., Arendt, J., Bradtke, J., de Ziegler, D. (1997) Determination of a dark-induced increase of pineal N-acetyl transferase activity and simultaneous radioimmunoassay of melatonin in pineal, serum and pituitary tissue of the male rat. J. Endocrinol. 72, 243–244.

    Google Scholar 

  51. 51.

    Wolden-Hanson, T., Mitton, D. R., McCants, R. L., Yellon, S. M., Wilkinson, C. W., Matsumoto, A. M., Rasmussen, D. D. (2000) Daily melatonin administration to middle-aged male rats suppresses body weight, intraabdominal adiposity, and plasma leptin and insulin independent of food intake and total body fat. Endocrinology 141, 487–497.

    CAS  PubMed  Google Scholar 

  52. 52.

    Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., Friedman, J. M. (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references


Supported in part by a Research Fund of Selcuk University Grant no: TF 2001/045. We would like to thank to Dr. Bayram Yilmaz of Firat University Medical School for his critical evaluation and English correction of the manuscript.

Author information



Corresponding author

Correspondence to A. K. Baltaci.

Rights and permissions

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Reprints and Permissions

About this article

Cite this article

Baltaci, A.K., Mogulkoc, R. Pinealectomy and Melatonin Administration in Rats: Their Effects on Plasma Leptin Levels and Relationship with Zinc. BIOLOGIA FUTURA 58, 335–343 (2007).

Download citation


  • Pinealectomy
  • melatonin administration
  • leptin
  • zinc