Increased litter size and suckling intensity inhibit KiSS-1 mRNA expression in rat arcuate nucleus

Document Type : Original Article

Authors

1 Department of Animal Sciences, College of Agriculture, Shiraz University, Shiraz, Iran

2 Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Transgenic Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Biotechnology Institute, College of Agriculture, Shiraz University, Shiraz, Iran

4 Biotechnology Institute, College of Agriculture, Shiraz University, Shiraz, Iran

Abstract

Objective(s): The effect of litter size and suckling intensity on the expression of KiSS-1 mRNA in the arcuate nucleus (ARC) of rats were evaluated.
Materials and Methods: Thirty two pregnant and four non-lactating ovariectomized (as control group) rats were used in this experiment. Lactating rats were allotted to eight equal groups. In three groups, litter size was adjusted to 5, 10, or 15 pups upon parturition and allowed to suckle their pups continuously by 8 days postpartum. In the other three groups, litter size was adjusted to five upon birth; the pups were separated from the dams for 6 hr on day 8 postpartum, after which the pups were allowed to suckle their dams for 2.5, 5, or 7.5 min prior to killing the dams. Two groups of lactating rats with either 10 or 15 pups were separated from their pups for 6 hr on day 8 postpartum, after which the pups were allowed to suckle their dams for 5 min before the dams were killed on day 8 postpartum. The ARC was removed and the expression of KiSS-1 mRNA was evaluated, using real-time PCR.
Results: The expression of KiSS-1 mRNA in the ARC was decreased as the litter size and intensity of suckling stimulus were increased. The effect of suckling intensity on the expression of KiSS-1 mRNA was more pronounced than that of litter size.
Conclusion: Increased litter size and suckling intensity decreased KiSS-1 mRNA expression in the ARC which may contribute to lactation anestrus in rat.

Keywords

References

1. Butler WR. Nutritional interactions with reproductive performance in dairy cattle. Anim Reprod Sci 2000; 60:449-457.
2. Fox SR, Smith MS. The suppression of pulsatile luteinizing hormone secretion during lactation in the rat. Endocrinology 1984; 115:2045-2051.
3. Maeda K-I, Tsukamura H, Uchida E, Ohkura N, Ohkura S, Yokoyama A. Changes in the pulsatile secretion of LH after the removal of and subsequent resuckling by pups in ovariectomized lactating rats. J Endocrinol 1989; 121:277-283.
4. Tsukamura H, Maeda KI, Ohkura S, Uchida E, Yokoyama A. The suppressing effect of the suckling stimulus on the pulsatile luteinizing hormone release is not mediated by prolactin in the rats at mid-lactation. Jpn J Anim Reprod 1991; 37:59-63.
5. Smith MS, Grove KL. Integration of the regulation of reproductive function and energy balance: lactation as a model. Front Neuroendocrinol 2002; 23:225-256.
6. Ohkura S, Uenoyama Y, Yamada S, Homma T, Takase K, Inoue N, et al. Physiological role of metastin/kisspeptin in regulating gonadotropin-releasing hormone (GnRH) secretion in female rats. Peptides 2009; 30:49-56.
7. Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS, Shagoury JK, et al. The GPR54 gene as a regulator of puberty. N Engl J Med 2003; 349:1614-1627.
8. Smith JT, Clarke IJ. Kisspeptin expression in the brain: catalyst for the initiation of puberty. Rev Endocr Metab Disord 2007; 8:1-9.
9. Roa J, Tena-Sempere M. KiSS-1 system and reproduction: comparative aspects and roles in the control of female gonadotropic axis in mammals. Gen Comp Endocrinol 2007; 153:132-140.
10. Seminara SB. We all remember our first kiss: kisspeptin and the male gonadal axis. J Clin Endocrinol Metab 2005; 90:6738-6740.
11. Navarro VM, Castellano JM, Fernández-Fernández R, Barreiro ML, Roa J, Sanchez-Criado JE, et al. Developmental and hormonally regulated messenger ribonucleic acid expression of KiSS-1 and its putative receptor, GPR54, in rat hypothalamus and potent luteinizing hormone-releasing activity of KiSS-1 peptide. Endocrinology 2004; 145:4565-4574.
12. Matsui H, Takatsu Y, Kumano S, Matsumoto H, Ohtaki T. Peripheral administration of metastin induces marked gonadotropin release and ovulation in the rat. Biochem Biophys Res Commun 2004; 320:383-388.
13. Roa J, Vigo E, Castellano JM, Navarro VM, Fernández-Fernández R, Casanueva FF, et al. Hypothalamic expression of KiSS-1 system and gonadotropin-releasing effects of kisspeptin in different reproductive states of the female Rat. Endocrinology 2006; 147:2864-2878.
14. Adachi S, Yamada S, Takatsu Y, Matsui H, Kinoshita M, Takase K, et al. Involvement of anteroventral periventricular metastin/kisspeptin neurons in estrogen positive feedback action on luteinizing hormone release in female rats. J Reprod Dev 2007; 53:367-378.
15. Smith JT, Cunningham MJ, Rissman EF, Clifton DK, Steiner RA. Regulation of kiss1 gene expression in the brain of the female mouse. Endocrinology 2005; 146:3686-3692.
16. Salehi MS, Jafarzadeh Shirazi MR, Zamiri MJ, Pazhoohi F, Namavar MR, Niazi A, et al. Hypothalamic expression of KiSS1 and RFamide-related peptide-3 mRNAs during the estrous cycle of rats. Int J Fertil Steril 2013; 6:304-309.
17. Yamada S, Uenoyama Y, Kinoshita M, Iwata K, Takase K, Matsui H, et al. Inhibition of metastin (kisspeptin-54)-GPR54 signaling in the arcuate nucleus-median eminence region during lactation in rats. Endocrinology 2007; 148:2226-2232.
18. Jiang Y, Berk M, Singh LS, Tan H, Yin L, Powell CT, et al. KiSS1 suppresses metastasis in human ovarian cancer via inhibition of protein kinase C alpha. Clin Exp Metastasis 2005; 22:369-376.
19. Lindblom C, Södersten P, Eneroth P. Effects of pup sucking behaviour on inhibition of sexual behaviour and ovulatory secretion of LH in lactating rats. J Endocrinol 1985; 104:419-425.
20. Janicki SM, Tsukamoto T, Salghetti SE, Tansey WP, Sachidanandam R, Prasanth KV, et al. From silencing to gene expression: real-time analysis in single cells. Cell 2004; 116:683-698.
21. Salehi MS, Namavar MR, Jafarzadeh Shirazi MR, Rahmanifar F, Tamadon A. A simple technique for separation of the anteroventral periventricular and arcuate nuclei in the rat hypothalamus. Anatomy 2014: In press.
22. Larionov A, Krause A, Miller W. A standard curve based method for relative real time PCR data processing. BMC Bioinformatics 2005; 6:62.
23. Livaka K, Schmittgen T. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods 2001; 25:402-408.
24. Roberts SB, Coward WA. Lactation increases the efficiency of energy utilization in rats. J Nutr 1984; 114:2193-2200.
25. Smith JT, Acohido BV, Clifton DK, Steiner RA. KiSS-1 neurones are direct targets for leptin in the ob/ob mouse. J Neuroendocrinol 2006; 18:298-303.
26. Castellano JM, Navarro VM, Fernandez-Fernandez R, Nogueiras R, Tovar S, Roa J, et al. Changes in hypothalamic KiSS-1 system and restoration of pubertal activation of the reproductive axis by kisspeptin in undernutrition. Endocrinology 2005; 146:3917-3925.
27. Johnstone LE, Higuchi T. Food intake and leptin during pregnancy and lactation. In: Russell JA, Douglas AJ, Windle RJ, Ingram CD, editors. Prog Brain Res. Vol 133. Elsevier; 2001.p. 215-227.
28. True C, Kirigiti MA, Kievit P, Grove KL, Smith MS. Leptin is not the critical signal for kisspeptin or luteinising hormone restoration during exit from negative energy balance. J Neuroendocrinol 2011; 23:1099-1112.
29. Caprio M, Fabbrini E, Isidori AM, Aversa A, Fabbri A. Leptin in reproduction. Trends Endocrinol Metab 2001; 12:65-72.
30. Kinsey-Jones JS, Li XF, Knox AMI, Wilkinson ES, Zhu XL, Chaudhary AA, et al. Down-regulation of hypothalamic kisspeptin and its receptor, Kiss1r, mRNA expression is associated with stress-induced suppression of luteinising hormone secretion in the female rat. J Neuroendocrinol 2008; 21:20-29.
31. Fischer D, Patchev VK, Hellbach S, Hassan AH, Almeida OF. Lactation as a model for naturally reversible hypercorticalism plasticity in the mechanisms governing hypothalamo-pituitary- adrenocortical activity in rats. J Clin Investig 1995; 96:1208-1215.
32. Vreeburg JTM, De Greef WJ, Ooms MP, Van Wouw P, Weber RFA. Effects of adrenocorticotropin and corticosterone on the negative feedback action of testosterone in the adult male rat. Endocrinology 1984; 115:977-983.
33. Mattheij JAM, Gruisen EFM, Swarts JJM. The suckling-induced rise of plasma prolactin in lactating rats: its dependence on stage of lactation and litter size. Horm Res Paediatr 1979; 11:325-336.
34. Kokay IC, Petersen SL, Grattan DR. Identification of prolactin-sensitive GABA and kisspeptin neurons in regions of the rat hypothalamus involved in the control of fertility. Endocrinology 2011; 152:526-535.
35. Sawai N, Iijima N, Takumi K, Matsumoto K,  Ozawa H. Immunofluorescent histochemical and ultrastructural studies on the innervation of
kisspeptin/neurokinin B neurons totubero-infundibular dopaminergic neurons in the arcuate nucleus of rats. Neurosci Res 2012; 74:10-16.
36. McNeilly A. Suckling and the control of gonadotropin secretion. In: Neill JD, editor. Knobil and Neill`s Physiology of Reproduction. 3. 3rd ed. St. Louis, MO, USA: Elsevier Academic Press; 2006. p. 2511-2536.
37. True C, Kirigiti M, Ciofi P, Grove KL, Smith MS. Characterisation of arcuate nucleus kisspeptin/neurokinin B neuronal projections and regulation during lactation in the rat. J Neuroendocrinol 2011; 23:52-64.
Iranian Journal of Basic Medical Sciences
Volume 17, Issue 8 - Serial Number 8
August 2014
Pages 600-605

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