The Effects of Melatonin Alone or in Combination with Zinc on Gonadotropin and Thyroid Hormones in Female Rats

Document Type : Original Articles

Authors

1 Department of Basic Science, Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran

2 Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

3 Department of Anatomy, Faculty of Medicine, Kurdistan of Medical Science, Sanandaj, Iran

4 Department of Clinical Science, Faculty of Veterinary Medicine, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran

10.32592/ARI.2023.78.6.1698

Abstract

Thyroid and gonadotropin hormones play an essential role in the regulation of regulating various physiological functions. The effects of melatonin and zinc (Zn) on these hormones have already been investigated. The aim of the present study was to investigate the effect of melatonin with and without zinc on the levels of gonadotropin hormones and thyroid hormones (triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH)) in female rats. In general, 35 sexually mature female rats were randomly divided into five treatment groups, with each group comprising 7 rats, in a completely randomized design (CRD) during the research. The rats were treated daily with Zn and melatonin via gavage as follows: T1 (control 1, basal diet), T2 (control 2, treatment with normal saline) and the other experimental groups, including T3, T4 and T5, were treated with Zn (40 ppm), melatonin (5 mg/kg) or a combination of Zn and melatonin at the same dose. The administration of the drugs was continued for 20 days (daily) . Plasma samples were then taken for the determination of LH, FFH, LH/FSH, estrogen, progesterone, T3, T4 and TSH levels. The results showed no significant differences in FSH and LH levels between treatments. Estrogen, progesterone and TSH levels were higher in the rats receiving 5 mg melatonin per day than in the other groups, but not statistically significant (P>0.05). However, T3 levels decreased significantly in the group receiving 40 mg/kg Zn compared to the other experiments. (P<0.05). The results showed no significant difference between the treatments in terms of T4 levels (P>0.05). In conclusion, no remarkable changes in other variables were observed in female rats receiving melatonin, Zn or a combination of melatonin and Zn, with the exception of T3.

Keywords

Main Subjects


References
1. Li Y, Yin Z, Zhang Y, Liu J, Cheng Y, Wang J, Pi F,
Zhang Y, Sun X. Perspective of Microbe-based
Minerals Fortification in Nutrition Security. Food Rev.
Int. 2022;38(3):268-81.
2. Harlow HJ. Influence of the pineal gland and melatonin
on blood flow and evaporative water loss during heat
stress in rats. J Pineal Res. 1987;4(2):147-59.
3. Bonior J, Jaworek J, Konturek SJ, Pawlik WW. Increase
of heat shock protein gene expression by melatonin in
AR42J cells. J Physiol Pharmacol. 2005;56(3):471.
4. Vittorio U, Emanuela R, Piero R, Silvia B. Effect of a
supplementation with myo-inositol plus melatonin on
oocyte quality in women who failed to conceive in
previousin vitrofertilization cycles for poor oocyte
quality: a prospective, longitudinal, cohort study.
Gynecol Endocrinol. 2011;27(11):857-61.
Nayeri Fasaei et al / Archives of Razi Institute, Vol. 78, No. 6 (2023) 1698-1708 1707
5. Lampiao F, Du Plessis SS. New developments of the
effect of melatonin on reproduction. World J Obstet
Gynecol. 2013;10;2(2):8-15.
6. Eryilmaz OG, Devran A, Sarikaya E, Aksakal FN,
Mollamahmutoğlu L, Cicek N. Melatonin improves the
oocyte and the embryo in IVF patients with sleep
disturbances, but does not improve the sleeping
problems. J Assist Reprod Genet. 2011;28:815-820.
7. Tamura H, Takasaki A, Taketani T, Tanabe M, Kizuka
F, Lee L, Tamura I, Maekawa R, Asada H, Yamagata
Y. Melatonin as a free radical scavenger in the ovarian
follicle. Endocr J. 2013; 60:1-13.
8. Kim MK, Park EA, Kim HJ, Choi WY, Cho JH, Lee
WS, Cha KY, Kim YS, Lee DR, Yoon TK. Does
supplementation of in-vitro culture medium with
melatonin improve IVF outcome in PCOS. Reprod
Biomed Online. 2013;26:22-29.
9. Lipovac MG. Antioxidative effect of melatonin on
human spermatozoa. Arch Androl. 2000;44(1):23-7.
10. Hapon MB, Simoncini M, Via G, Jahn GA. Effect of
hypothyroidism on hormone profiles in virgin, pregnant
and lactating rats, and on lactation. Reprod.
2003;126(3):371-82.
11. Tordjman S, Chokron S, Delorme R, Charrier A,
Bellissant E, Jaafari N, Fougerou C. Melatonin:
pharmacology, functions and therapeutic benefits. Curr
Neuropharmacol. 2017;15(3):434-43.
12. Adah Sylvanus A, Adah Arimie D, Nwonuma Charles
O, Oyekunle T, Olaosebikan B. Melatonin modulates
haematological and water quality parameters following
a 100 km transportation of Clarias gariepinus by road.
Iran J Vet Med. 2022. doi: 10.22059/ijvm.2022.
348436.1005310
13. Zawilska JB, Skene DJ, Arendt J. Physiology and
pharmacology of melatonin in relation to biological
rhythms. Pharmacol Rep. 2009;61(3):383-410.
14. Maciel LM, Magalhães PK. Thyroid and pregnancy.
Arq Bras Endocrinol Metabol. 2008;52:1084-95.
15. Maganhin CC, Fuchs LF, Simões RS, Oliveira-Filho
RM, de Jesus Simões M, Baracat EC, Soares Jr JM.
Effects of melatonin on ovarian follicles. Eur J Obstet
Gynecol. 2013;166(2):178-84.
16. Tamura H, Takasaki A, Miwa I, Taniguchi K, Maekawa
R, Asada H, Taketani T, Matsuoka A, Yamagata Y,
Shimamura K, Morioka H. Oxidative stress impairs
oocyte quality and melatonin protects oocytes from free
radical damage and improves fertilization rate. J Pineal
Res. 2008;44(3):280-7.
17. Yilmaz M, Mogulkoc R, Baltaci AK. Effect of threeweek zinc and melatonin supplementation on the
oxidant-antioxidant system in experimental renal
ischemia-reperfusion in rats. Acta Clin Croat.
2015;54(4).
18. Veldhuis JD, Liem AY, South S, Weltman A, Weltman
J, Clemmons DA, Abbott R, Mulligan T, Johnson ML,
Pincus S. Differential impact of age, sex steroid
hormones, and obesity on basal versus pulsatile growth
hormone secretion in men as assessed in an
ultrasensitive chemiluminescence assay. J Clin
Endocrinol Metab. 1995;80(11):3209-22.
19. Shah N, Evans WS, Veldhuis JD. Actions of estrogen
on pulsatile, nyctohemeral, and entropic modes of
growth hormone secretion. Am J Physiol Regul Integr
Comp Physiol. 1999;276(5):R1351-8.
20.Caufriez A, Leproult R, L'Hermite-Balériaux M,
Kerkhofs M, Copinschi G. Progesterone prevents sleep
disturbances and modulates GH, TSH, and melatonin
secretion in postmenopausal women. J Clin Endocrinol
Metab. 2011;96(4):E614-23.
21. Nasiadek M, Stragierowicz J, Klimczak M, Kilanowicz
A. The role of zinc in selected female reproductive
system disorders. Nutrients. 2020;12(8):2464.
22. Garner TB, Hester JM, Carothers A, Diaz FJ. Role
of zinc in female reproduction. Biol Reprod.
2021;104(5):976-994.
23. Yong W, Ma H, Na M, Gao T, Zhang Y, Hao L, Yu H,
Yang H, Deng X. Roles of melatonin in the field
of reproductive medicine. Biomed Pharmacother.
2021;144:112001.
24. Moustafa SA. Effect of glutathione (GSH) depletion on
the serum levels of triiodothyronine (T3), thyroxine
(T4), and T3/T4 ratio in allyl alcohol-treated male rats
and possible protection with zinc. Int J Toxicol.
2001;20(1):15-20.
25. Piao F, Yokoyama K, Ma N, Yamauchi T. Subacute
toxic effects of zinc on various tissues and organs of
rats. Toxicol Lett. 2003;145(1):28-35.
26.Chaurasia SS, Gupta P, Kar A, Maiti PK. Lead induced
thyroid dysfunction and lipid peroxidation in the fish
Clarias batrachus with special reference to hepatic type
I-5′-monodeiodinase activity. Bull Environ Contam
Toxicol. 1996;56:649-654.
27. Todini L. Thyroid hormones in small ruminants: effects
of endogenous, environmental and nutritional factors.
Animal. 2007;1(7):997-1008.
28. Silva JF, Ocarino NM, Serakides R. Thyroid hormones
1708 Nayeri Fasaei et al / Archives of Razi Institute, Vol. 78, No. 6 (2023) 1698-1708
and female reproduction. Biol Reprod. 2018;99(5):907-
921.
29. Webb SM, Puig‐Domingo M. Role of melatonin in
health and disease. Clin Endocrinol. 1995;42(3):221-34.
30. Zang LY, Cosma G, Gardner H, Vallyathan V.
Scavenging of reactive oxygen species by melatonin.
Biochim Biophys Acta Gen Subj. 1998;1425(3):469-77.
31.Reiter RJ, Tan DX, Osuna C, Gitto E. Actions of
melatonin in the reduction of oxidative stress. J Biomed
Sci. 2000;7(6):444-58.
32. Escames G, Ozturk G, Baño‐Otálora B, Pozo MJ, Madrid
JA, Reiter RJ, Serrano E, Concepción M,
Acuña‐Castroviejo D. Exercise and melatonin in humans:
reciprocal benefits. J pineal res. 2012;52(1):1-1.
33. Webley GE, Luck MR. Melatonin directly stimulates
the secretion of progesterone by human and bovine
granulosa cells in vitro. Reprod. 1986;78(2):711-7.
34. Webley GE, Luck MR, Hearn JP. Stimulation of
progesterone secretion by cultured human granulosa
cells with melatonin and catecholamines. Reprod.
1988;84(2):669-77.
35. Niles LP, Wang J, Shen L, Lobb DK, Younglai EV.
Melatonin receptor mRNA expression in human
granulosa cells. Mol Cell Endocrinol. 1999;156(1-
2):107-10.
36. Woo MM, Tai CJ, Kang SK, Nathwani PS, Pang SF,
Leung PC. Direct action of melatonin in human
granulosa-luteal cells. J Clin Endocrinol Metab.
2001;86(10):4789-97.
37. Taketani T, Tamura H, Takasaki A, Lee L, Kizuka F,
Tamura I, Taniguchi K, Maekawa R, Asada H,
Shimamura K, Reiter RJ. Protective role of melatonin in
progesterone production by human luteal cells. J pineal
res. 2011;51(2):207-13.
38. Cipolla-Neto J, Amaral FG, Soares Jr JM, Gallo CC,
Furtado A, Cavaco JE, Gonçalves I, Santos CR, Quintela
T. The crosstalk between melatonin and sex steroid
hormones. Neuroendocrinol. 2022;112(2):115-29.
39. Tamura H, Jozaki M, Tanabe M, Shirafuta Y, Mihara Y,
Shinagawa M, Tamura I, Maekawa R, Sato S, Taketani
T, Takasaki A. Importance of melatonin in assisted
reproductive technology and ovarian aging. Int J Mol
Sci. 2020;21(3):1135.
40. D’Angelo G, Marseglia L, Manti S, Colavita L, Cuppari
C, Impellizzeri P, Arena S, Arrigo T, Salpietro C, Gitto
E. Atopy and autoimmune thyroid diseases: melatonin
can be useful? Ital J Pediatr. 2016;42:1-6.
41. De Leo S, Lee SY, Braverman LE. Hyperthyroidism.
The Lancet. 2016;388(10047):906-918.
42. Díez JJ, Iglesias P. Spontaneous subclinical
hypothyroidism in patients older than 55 years: an
analysis of natural course and risk factors for the
development of overt thyroid failure. J Clin Endocrinol
Metab. 2004;89(10):4890-7.
43. Kaklamanos I, Zarokosta M, Flessas I, Zoulamoglou M,
Katsoulas T, Birbas K, Troupis T, Mariolis-Sapsakos T.
Surgical anatomy of double pyramidal lobe on total
thyroidectomy: a rare case report. J Surg Case Rep.
2017;2017(3):rjx035.
44. Üstündağ H, Şentürk E, Gül M. Melatonin and
hyperthyroidism. Arch Basic Clin Res. 2020;2(2):59-64.
45. Laskar P, Acharjee S, Singh SS. Effect of Exogenous
Melatonin on Thyroxine (T 4), Thyrotropin (TSH)
Hormone Levels and Expression patterns of Melatonin
Receptor (MT1 and MT2) Proteins on Thyroid gland
during Different age groups of Male and Female Swiss
albino Mice. Adv biores. 2015;6(1).
46.Badi N, Fazelipour S, Naji T, Babaei M, Kalantari
Hesari A. Histomorphometric and Biochemical Study of
Liver and Thyroid Hormones Following Administration
of MoO3 Nanoparticles in Female Rats. Iran J Vet Med.
2022; 16(2): 188-201. doi: 10.22059/ijvm.2021.330872.
1005196
47.Chowdhury VS, Yamamoto K, Ubuka T, Bentley GE,
Hattori A, Tsutsui K. Melatonin stimulates the release
of gonadotropin-inhibitory hormone by the avian
hypothalamus. Endocrinol. 2010;151(1):271-80.
48. Khanam S. Impact of zinc on thyroid metabolism. J
Diabetes Metab Disord Control. 2018;5(1):27-8.