Influences of Serotonin Hydrochloride on Adiponectin, Ghrelin and KiSS1 Genes Expression

Authors

  • Fariba Mahmoudi 1. Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
  • Khadijeh Haghighat Gollo 1. Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran

DOI:

https://doi.org/10.31661/gmj.v9i.1767

Keywords:

Serotonin; Kisspeptin; Ghrelin; Adiponectin

Abstract

Background: Serotonin and kisspeptin stimulates gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) release while ghrelin and adiponectin inhibit them. In the present experimental study, the effects of central injection of serotonin were investigated on LH concentration, KiSS1, adiponectin, and ghrelin genes expression. Materials and Methods: Fifteen Wistar male rats in three groups received saline or serotonin hydrochloride via the third cerebral ventricle. Blood samples were collected via the tail vein. Serum LH concentration and relative gene expression were evaluated by radioimmunoassay and real-time polymerase chain reaction method, respectively. Results: Serotonin significantly increased the mean serum LH concentration and  KiSS1 gene expression levels compared to the saline group. Serotonin significantly decreased the mean ghrelin and adiponectin genes expression levels compared to the saline group. Conclusion: The serotonergic pathway may have stimulatory effects on hypothalamic kisspeptin synthesis, partly via inhibiting hypothalamic ghrelin and adiponectin neural activity.[GMJ.2020;9:e1767]



References

Feijó Fde M, Bertoluci MC, Reis C. Serotonin and hypothalamic control of hunger: a review. Rev Assoc Med Bras. 2011; 57(1): 74-7. https://doi.org/10.1016/S0104-4230(11)70020-3 Leibowitz SF, Alexander JT. Hypothalamic serotonin in control of eating behavior, meal size, and body weight. Biol Psychiatry. 1998; 44(9): 851-64. https://doi.org/10.1016/S0006-3223(98)00186-3 Mawe GM, Hoffman JM. Serotonin signaling in the gastrointestinal tract: functions, dysfunctions, and therapeutic targets. Nat Rev Gastroenterol Hepatol. 2013; 10(8): 473-86. https://doi.org/10.1038/nrgastro.2013.105PMid:23797870 PMCid:PMC4048923 Campos MB, Vitale ML, Calandra RS, Chiocchio SR. Serotonergic innervation of the rat testis. J Reprod Fertil. 1990; 88(2): 475-9. https://doi.org/10.1530/jrf.0.0880475PMid:2325015 Prasad P, Ogawa S, Parhar IS. Serotonin reuptake inhibitor citalopram inhibits GnRH synthesis and spermatogenesis in the male zebrafish. Biol Reprod. 2015; 93(4):1-10. https://doi.org/10.1095/biolreprod.115.129965PMid:26157069 Kim HS, Yumkham S, Choi JH, Son GH, Kim K, Ryu SH, Suh PG. Serotonin stimulates GnRH secretion through the c-Src-PLC gamma1 pathway in GT1-7 hypothalamic cells. J Endocrinol. 2006; 190(3): 581-91. https://doi.org/10.1677/joe.1.06727PMid:17003259 Thompson EL, Patterson M, Murphy KG, Smith KL, Dhillo WS, Todd JF, et al. Central and peripheral administration of kisspeptin-10 stimulates the hypothalamic-pituitary-gonadal axis. J Neuroendocrinol. 2004; 16(10): 850-8. https://doi.org/10.1111/j.1365-2826.2004.01240.xPMid:15500545 Meczekalski B, Katulski K, Podfigurna-Stopa A, Czyzyk A, Genazzani AD. Spontaneous endogenous pulsatile release of kisspeptin is temporally coupled with luteinizing hormone in healthy women. Fertil Steril. 2016; 105(5):1345-50. https://doi.org/10.1016/j.fertnstert.2016.01.029PMid:26859129 Roseweir AK, Kauffman AS, Smith JT, Guerrier KA, Morgan K, Pielecka-Fortuna J, et al. Discovery of potent kisspeptin antagonists delineate physiological mechanisms of gonadotropin regulation. J Neurosci. 2009; 29(12): 3920-9. https://doi.org/10.1523/JNEUROSCI.5740-08.2009PMid:19321788 PMCid:PMC3035813 de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E, et al. Hypogonadotropic hypogonadism due to loss of function of the Kiss1-derived peptide receptor GPR54. Proc Natl Acad Sci USA. 2003; 100(19): 10972-6. https://doi.org/10.1073/pnas.1834399100PMid:12944565 PMCid:PMC196911 Maleszka A, Smolinska N, Nitkiewicz A, Chojnowska K, Dobrzyn K. Adiponectin exprisson in the porcin ovary during the oestrous cycle and its effect on ovarian steroidogenes. Int J Endocrinol. 2014; 2014: 957076. https://doi.org/10.1155/2014/957076PMid:24790602 PMCid:PMC3984813 Dobrzyn K, Smolinska N, Kiezun M, Szeszko k, Rytelewska E, Kisielewska K, et al. Adiponectin: a new regulator of female reproductive system. Int J Endocrinol. 2018; 2018: 7965071. https://doi.org/10.1155/2018/7965071PMid:29853884 PMCid:PMC5949163 Itoh H, Kawano Y, Furukawa Y, Matsumoto H, Yuge A, Narahara H. The role of serum adiponectin levels in women with polycystic ovarian syndrome. Clin Exp Obstet Gynecol. 2013; 40(4): 531-5. Kluge M, Schüssler P, Schmidt D, Uhr M, Steiger A.Ghrelin suppresses secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in women. J Clin Endocrinol Metab. 2012; 97(3): 448-51. https://doi.org/10.1210/jc.2011-2607PMid:22259063 Mahmoudi F. Kisspeptin increases luteinizing hormone secretion in food deprived D-Lys3-GHRP6-treated rats. GMJ. 2017; 6(1): 39-46 Ogawa S, Ng KW, Ramadasan PN, Nathan FM, Parhar IS. Habenular Kiss1 neurons modulate the serotonergic system in the brain of zebrafish. Endocrinology. 2016; 153(5): 2398-7. https://doi.org/10.1210/en.2012-1062PMid:22454151 Fujitsuka N, Asakawa A, Hayashi M, Sameshima M, Amitani H, Kojima S, et al. Selective serotonin reuptake inhibitors modify physiological gastrointestinal motor activities via 5-HT2c receptor and acyl ghrelin. Biol Psychiatry. 2009; 65(9): 748-59. https://doi.org/10.1016/j.biopsych.2008.10.031PMid:19058784 Nonogaki K, Ohashi-Nozue K, Oka Y. A negative feedback system between brain serotonin systems and plasma active ghrelin levels in mice. Biochem Biophys Res Commun. 2006; 341(3): 703-7. https://doi.org/10.1016/j.bbrc.2006.01.021PMid:16430857 Lee MD, Somerville E, Kennett GA, Dourish CT, Clifton PG. Reduced hypophagic effects of d-fenfluramine and the 5-HT2C receptor agonist mCPP in 5-HT1B receptor knockout mice. Psychopharmacology. 2004; 176(1): 39-49. https://doi.org/10.1007/s00213-004-1864-0PMid:15138762 Halford JC, Harrold JA. 5-HT(2C) receptor agonists and the control of appetite. Handb Exp Pharmacol. 2012; 209: 349-56. https://doi.org/10.1007/978-3-642-24716-3_16PMid:22249823 Manfredi-Lozano M, Roa J, Ruiz-Pino F, Piet R, Garcia-Galiano D, Pineda R et al. Defining a novel leptin-melanocortin-kisspeptin pathway involved in the metabolic control of puberty. Mol Metab. 2016; 5(10): 844-57. https://doi.org/10.1016/j.molmet.2016.08.003PMid:27688998 PMCid:PMC5034608 Goto M, Arima H, Watanabe M, Hayashi M, Banno R, Sato I, et al. Ghrelin increases neuropeptide Y and agouti-related peptide gene expression in the arcuate nucleus in rat hypothalamic organotypic cultures. Endocrinology. 2006; 147(11): 5102-9. https://doi.org/10.1210/en.2006-0104PMid:16887908 Olszewski PK, Bomberg EM, Grace MK, Levine AS. Alpha-melanocyte stimulating hormone and ghrelin: central interaction in feeding control. Peptides. 2007; 28(10): 2084-9. https://doi.org/10.1016/j.peptides.2007.07.017PMid:17719137 Forbes S, Li XF, Kinsey-Jones J, O'Byrne K. Effects of ghrelin on Kisspeptin mRNA expression in the hypothalamic medial preoptic area and pulsatile luteinising hormone secretion in the female rat. Neurosci Lett. 2009; 460(2): 143-7. https://doi.org/10.1016/j.neulet.2009.05.060PMid:19477231 Fu LY, van den Pol AN. Kisspeptin directly excites anorexigenic proopiomelanocortin neurons but inhibits orexigenic neuropeptide Y cells by an indirect synaptic mechanism. J Neurosci. 2010; 30(30): 10205-9. https://doi.org/10.1523/JNEUROSCI.2098-10.2010PMid:20668204 PMCid:PMC2933146 Mahmoodzadeh M, Azarpira N, Yaghobi R. The Effect of leptin and adiponectin on KiSS-1 and KissR mRNA expression in rat islets of langerhans and CRI-D2 cell line. Int J Endocrinol Metab. 2014; 12(2): 1-6. https://doi.org/10.5812/ijem.15297PMid:24910643 PMCid:PMC4030219 Shosaku N, Akira SH, Seitarou O, Toshiji L. 5-HT2A receptor antagonist increases circulating adiponectin in patients with type 2 diabetes. Blood Coagul Fibrinolysis. 2005; 16 (6): 423-38. https://doi.org/10.1097/01.mbc.0000176197.48134.08PMid:16093733 Wen JP, Lv WS, Yang J, Nie AF, Cheng XB, Yang Y, et al. Globular adiponectin inhibits GnRH secretion from GT1-7 hypothalamic GnRH neurons by induction of hyperpolarization of membrane potential. Biochem Biophys Res Commun. 2008;371(4):756-61. https://doi.org/10.1016/j.bbrc.2008.04.146PMid:18466765 Lu M, Tang Q, Olefsky JM, Mellon PL, Webster NJ. Adiponectin activates adenosine monophosphate-activated protein kinase and decreases luteinizing hormone secretion in LbetaT2 gonadotropes. Mol Endocrinol. 2008; 22(3): 760-71. https://doi.org/10.1210/me.2007-0330PMid:18006641 PMCid:PMC2262174 Li HY, Chiu YF, Hwu CM, Sheu WH, Hung YJ, Fujimoto W. The negative correlation between plasma adiponectin and blood pressure depends on obesity: a family-based association study in SAPPHIRe. Am J Hypertens. 2008; 21(4): 471-6. https://doi.org/10.1038/ajh.2008.5PMid:18369365

Published

2020-09-07

How to Cite

Mahmoudi, F., & Haghighat Gollo, K. (2020). Influences of Serotonin Hydrochloride on Adiponectin, Ghrelin and KiSS1 Genes Expression: . Galen Medical Journal, 9, e1767. https://doi.org/10.31661/gmj.v9i.1767

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