Changes in the content of luteinizing and follicle-stimulating hormones in the gonads of Danio rerio fish under the action of a synthetic analogue of kisspeptin 1

Abstract

BACKGROUND: Kisspeptin 1 plays a significant role in regulating the activity of the hypothalamic-pituitary-gonadal axis. It is known it interacts directly with gonadotropin-releasing hormone by stimulating its secretion in the hypothalamus and thus affecting downstream sex hormones via gonadotropins, but the exact mechanism of kisspeptin 1 effects on follicle-stimulating and luteinizing hormones is poorly understood.

AIM: To investigate the effects of a synthetic kisspeptin 1 analog on follicle-stimulating and luteinizing hormone levels in the gonads of Danio rerio.

MATERIALS AND METHODS: The study involved 84 sexually mature Danio rerio females after spawning. The model animals were anesthetized with lidocaine and synthetic analog of kisspeptin 1, 0.9% sodium chloride solution were administered intracerebrally in doses of 2, 8 µg/kg. After 1 or 4 hours, follicle-stimulating and luteinizing hormone’s levels were measured using enzyme immunoassay.

RESULTS: A statistically significant increase in follicle-stimulating hormone levels occurs at a dose of 8 µg/kg after 1 and 4 hours and at a dose of 2 µg/kg 4 hours after injection relative to the corresponding control groups. An increase in luteinizing hormone’s production was also recorded at a dose of 8 μg/kg after 1 and 4 hours of exposure compared with the control. Elevated follicle-stimulating and luteinizing hormone’s levels were also recorded at a dose of 8 μg/mg and exposure for 1 hour relative to a dose of 2 μg/kg at the same resting time. Without taking into account the time exposure, the administration of synthetic analog of kisspeptin 1 at a dose of 8 µg/kg leads to an increased level of both hormones, and a dose of 2 µg/kg contributes to an increase in luteinizing hormone’s level.

CONCLUSIONS: The obtained results contribute to the study of pharmacological functions of synthetic analog of kisspeptin 1 and in the future can be used for therapeutic purposes in the treatment of diseases of the gonadal system.

Keywords

synthetic kisspeptin 1 analog / Danio rerio / luteinizing hormone / follicle-stimulating hormone / hypothalamic-pituitary-gonadal axis

References

[1] Mills EG, Yang L, Abbara A, et al. Current perspectives on kisspeptins role in behavior. Front Endocrinol (Lausanne). 2022;13:928143. doi: 10.3389/fendo.2022.928143

[2] Mills E.G., Yang L., Abbara A., et al. Current perspectives on kisspeptins role in behaviour // Front Endocrinol (Lausanne). 2022. Vol. 13. P. 928143. doi: 10.3389/fendo.2022.928143

[3] López-Ojeda W, Hurley RA. Kisspeptin in the limbic system: New insights into its neuromodulatory roles. J Neuropsychiatry Clin Neurosci. 2022;34(3):190–195. doi: 10.1176/appi.neuropsych.20220087

[4] López-Ojeda W., Hurley R.A. Kisspeptin in the limbic system: New insights into its neuromodulatory roles // J Neuropsychiatry Clin Neurosci. 2022. Vol. 34, N 3. P. 190–195. doi: 10.1176/appi.neuropsych.20220087

[5] Xie Q, Kang Y, Zhang C, et al. The role of kisspeptin in the control of the hypothalamic-pituitary-gonadal axis and reproduction. Front Endocrinol. 2022;13:925206. doi: 10.3389/fendo.2022.925206

[6] Xie Q., Kang Y., Zhang C., et al. The role of kisspeptin in the control of the hypothalamic-pituitary-gonadal axis and reproduction // Front Endocrinol. 2022. Vol. 13. P. 925206. doi: 10.3389/fendo.2022.925206

[7] Ogawa S, Parhar IS. Biological significance of kisspeptin–kiss 1 receptor signaling in the habenula of teleost species. Front Endocrinol (Lausanne). 2018;9:222. doi: 10.3389/fendo.2018.00222

[8] Ogawa S., Parhar I.S. Biological significance of kisspeptin–kiss 1 receptor signaling in the habenula of teleost species // Front Endocrinol (Lausanne). 2018. Vol. 9. P. 222. doi: 10.3389/fendo.2018.00222

[9] Ogawa S, Ng KW, Ramadasan PN, et al. Habenular Kiss1 neurons modulate the serotonergic system in the brain of zebrafish. Endocrinology. 2012;153(5):2398–2407. doi: 10.1210/en.2012-1062

[10] Ogawa S., Ng K.W., Ramadasan P.N., et al. Habenular Kiss1 neurons modulate the serotonergic system in the brain of zebrafish // Endocrinology. 2012. Vol. 153, N 5. P. 2398–2407. doi: 10.1210/en.2012-1062

[11] Onuma TA, Duan C. Duplicated Kiss1 receptor genes in zebrafish: distinct gene expression patterns, different ligand selectivity, and a novel nuclear isoform with transactivating activity. FASEB J. 2012;26(7):2941–2950. doi: 10.1096/fj.11-201095

[12] Onuma T.A., Duan C. Duplicated Kiss1 receptor genes in zebrafish: distinct gene expression patterns, different ligand selectivity, and a novel nuclear isoform with transactivating activity // FASEB J. 2012. Vol. 26, N 7. P. 2941–2950. doi: 10.1096/fj.11-201095

[13] Zhao Y, Lin MC, Mock A, et al. Kisspeptins modulate the biology of multiple populations of gonadotropin-releasing hormone neurons during embryogenesis and adulthood in zebrafish (Danio rerio). PLoS One. 2014;9(8):e104330. doi: 10.1371/journal.pone.0104330

[14] Zhao Y., Lin M.C., Mock A., et al. Kisspeptins modulate the biology of multiple populations of gonadotropin-releasing hormone neurons during embryogenesis and adulthood in zebrafish (Danio rerio) // PLoS One. 2014. Vol. 9, N 8. P. e104330. doi: 10.1371/journal.pone.0104330

[15] Song Y, Chen J, Tao B. Kisspeptin2 regulates hormone expression in female zebrafish (Danio rerio) pituitary. Mol Cell Endocrinol. 2020;513:110858. doi: 10.1016/j.mce.2020.110858

[16] Song Y., Chen J., Tao B. Kisspeptin2 regulates hormone expression in female zebrafish (Danio rerio) pituitary // Mol Cell Endocrinol. 2020. Vol. 513. P. 110858. doi: 10.1016/j.mce.2020.110858

[17] Sivalingam M., Parhar I.S. Hypothalamic kisspeptin and kisspeptin receptors: Species variation in reproduction and reproductive behaviours. Front Neuroendocrinol. 2022;64:100951. doi: 10.1016/j.yfrne.2021.100951

[18] Sivalingam M., Parhar I.S. Hypothalamic kisspeptin and kisspeptin receptors: Species variation in reproduction and reproductive behaviours // Front Neuroendocrinol. 2022. Vol. 64. P. 100951. doi: 10.1016/j.yfrne.2021.100951

[19] Hatef A, Rajeswari JJ, Unniappan S. Kisspeptin stimulates oocyte maturation, and food deprivation modulates the abundance of kisspeptin system in zebrafish gonads. Aquaculture and Fisheries. 2022;7(5):484–493. EDN: JSFWAV doi: 10.1016/j.aaf.2022.02.003

[20] Hatef A., Rajeswari J.J., Unniappan S. Kisspeptin stimulates oocyte maturation, and food deprivation modulates the abundance of kisspeptin system in zebrafish gonads // Aquaculture and Fisheries. 2022. Vol. 7, N 5. P. 484–493. EDN: JSFWAV doi: 10.1016/j.aaf.2022.02.003

[21] Hoo JY, Kumari Y, Shaikh MF, et al. Zebrafish: a versatile animal model for fertility research. Biomed Res Int. 2016;2016:9732780. doi: 10.1155/2016/9732780

[22] Hoo J.Y., Kumari Y., Shaikh M.F., et al. Zebrafish: A versatile animal model for fertility research // Biomed Res Int. 2016. Vol. 2016. P. 9732780. doi: 10.1155/2016/9732780

[23] Zhang Z, Zhu B, Ge W. Genetic analysis of zebrafish gonadotropin (FSH and LH) functions by TALEN-mediated gene disruption. Mol Endocrinol. 2014;29(1):76–98. doi: 10.1210/me.2014-1256

[24] Zhang Z., Zhu B., Ge W. Genetic analysis of zebrafish gonadotropin (FSH and LH) functions by TALEN-mediated gene disruption // Mol Endocrinol. 2014. Vol. 29, N 1. P. 76–98. doi: 10.1210/me.2014-1256

[25] Ogawa S, Nathan FM, Parhar IS. Habenular kisspeptin modulates fear in the zebrafish. Proc Natl Acad Sci U S A. 2014; 111(10):3841-3846. doi: 10.1073/pnas.1314184111.

[26] Ogawa S., Nathan F.M., Parhar I.S. Habenular kisspeptin modulates fear in the zebrafish // Proc Natl Acad Sci U S A. 2014. Vol. 111, No. 10. P. 3841–3846. doi: 10.1073/pnas.1314184111

[27] Panent RUS No. 2766689 C1/15.03.2022, under application No. 2020144338A. Blazhenko AA, Khohlov PP, Lebedev AA, Shabanov PD. Application of lidocaine for anesthesia of the model organism Danio rerio in experimental conditions. Available from: https://patents.google.com/patent/RU2766689C1/ru. Accessed: 31 Oct 2024. (In Russ.)

[28] Патент РФ на изобретение № 2766689 C1/15.03.2022. Бюл. № 2020144338А. Блаженко А.А., Хохлов П.П., Лебедев А.А., Шабанов П.Д. Применение лидокаина для анестезии модельного организма Danio rerio в экспериментальных условиях. Режим доступа: https://patents.google.com/patent/RU2766689C1/ru. Дата обращения: 31.10.2024.

[29] Kitahashi T, Ogawa S, Parhar IS. Cloning and expression of Kiss2 in the zebrafish and medaka. Endocrinology. 2009;150(2):821–831. doi: 10.1210/en.2008-0940

[30] Kitahashi T., Ogawa S., Parhar I.S. Cloning and expression of Kiss2 in the zebrafish and medaka // Endocrinology. 2009. Vol. 150, N 2. P. 821–831. doi: 10.1210/en.2008-0940

[31] Matsui H, Takatsu Y, Kumano S, et al. Peripheral administration of metastin induces marked gonadotropin release and ovulation in the rat. Biochem Biophys Res Commun. 2004;320(2):383–388. doi: 10.1016/j.bbrc.2004.05.185

[32] Matsui H., Takatsu Y., Kumano S., et al. Peripheral administration of metastin induces marked gonadotropin release and ovulation in the rat // Biochem Biophys Res Commun. 2004. Vol. 320, N 2. P. 383–388. doi: 10.1016/j.bbrc.2004.05.185

[33] Shahab M, Mastronardi C, Seminara SB, et al. Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates. Proc Natl Acad Sci USA. 2005;102(6):2129–2134. doi: 10.1073/pnas.0409822102

[34] Shahab M., Mastronardi C., Seminara S.B., et al. Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates // Proc Natl Acad Sci USA. 2005. Vol. 102, N 6. P. 2129–2134. doi: 10.1073/pnas.0409822102

[35] Roa J, Vigo E, Garcia-Galiano D, et al. Desensitization of gonadotropin responses to kisspeptin in the female rat: analyses of LH and FSH secretion at different developmental and metabolic states. Am J Physiol Endocrinol Metab. 2008;294(6):1088–1096. doi: 10.1152/ajpendo.90240.2008

[36] Roa J., Vigo E., Garcia-Galiano D., et al. Desensitization of gonadotropin responses to kisspeptin in the female rat: analyses of LH and FSH secretion at different developmental and metabolic states // Am J Physiol Endocrinol Metab. 2008. Vol. 294, N 6. P. 1088–1096. doi: 10.1152/ajpendo.90240.2008

[37] Ezzat Ahmed A, Saito H, Sawada T, et al. Characteristics of the stimulatory effect of kisspeptin-10 on the secretion of luteinizing hormone, follicle-stimulating hormone and growth hormone in prepubertal male and female cattle. J Reprod Dev. 2009;5:650–654. doi: 10.1262/jrd.20255

[38] Ezzat Ahmed A., Saito H., Sawada T., et al. Characteristics of the stimulatory effect of kisspeptin-10 on the secretion of luteinizing hormone, follicle-stimulating hormone and growth hormone in prepubertal male and female cattle // J Reprod Dev. 2009. Vol. 55. P. 650–654. doi: 10.1262/jrd.20255

[39] Burow S, Fontaine R, von Krogh K, et al. Medaka follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh): Developmental profiles of pituitary protein and gene expression levels. Gen Comp Endocrinol. 2019;272:93–108. doi: 10.1016/j.ygcen.2018.12.006

[40] Burow S., Fontaine R., von Krogh K., et al. Medaka follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh): Developmental profiles of pituitary protein and gene expression levels // Gen Comp Endocrinol. 2019. Vol. 272. P. 93–108. doi: 10.1016/j.ygcen.2018.12.006

[41] Zhang Z, Lau SW, Zhang L, Ge W. Disruption of zebrafish follicle-stimulating hormone receptor (FSHR) but not luteinizing hormone receptor (LHCGR) gene by Talen leads to failed follicle activation in females followed by sexual reversal to males. Endocrinology. 2015;156(10):3747–3762. doi: 10.1210/en.2015-1039

[42] Zhang Z., Lau S.W., Zhang L., Ge W. Disruption of zebrafish follicle-stimulating hormone receptor (FSHR) but not luteinizing hormone receptor (LHCGR) gene by talen leads to failed follicle activation in females followed by sexual reversal to males // Endocrinology. 2015. Vol. 156, N 10. P. 3747–3762. doi: 10.1210/en.2015-1039

[43] Zmijewska A, Czelejewska W, Drzewiecka EM, Franczak A. Effect of kisspeptin (KISS) and RFamide-related peptide-3 (RFRP-3) on the synthesis and secretion of FSH in vitro by pituitary cells in pigs. Theriogenology. 2021;171:72–84. doi: 10.1016/j.theriogenology.2021.05.010

[44] Zmijewska A., Czelejewska W., Drzewiecka E.M., Franczak A. Effect of kisspeptin (KISS) and RFamide-related peptide-3 (RFRP-3) on the synthesis and secretion of FSH in vitro by pituitary cells in pigs // Theriogenology. 2021. Vol. 171. P. 72–84. doi: 10.1016/j.theriogenology.2021.05.010

[45] Messager S, Chatzidaki EE, Ma D, et al. Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc Natl Acad Sci USA. 2005;102(5):1761–1766. doi: 10.1073/pnas.0409330102

[46] Messager S., Chatzidaki E.E., Ma D., et al. Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54 // Proc Natl Acad Sci USA. 2005. Vol. 102, N 5. P. 1761–1766. doi: 10.1073/pnas.0409330102

[47] Li J, Cheng CHK. Evolution of gonadotropin signaling on gonad development: insights from gene knockout studies in zebrafish. Biol Rep. 2018;99(4):686–694. doi: 10.1093/biolre/ioy101

[48] Li J., Cheng C.H.K. Evolution of gonadotropin signaling on gonad development: insights from gene knockout studies in zebrafish // Biol Rep. 2018. Vol. 99, N 4. P. 686–694. doi: 10.1093/biolre/ioy101

[49] Leonardi CEP, Carrasco RA, Dias FCF, et al. Mechanism of LH release after peripheral administration of kisspeptin in cattle. PLoS One. 2022;17(12):e0278564. doi: 10.1371/journal.pone.0278564

[50] Leonardi C.E.P, Carrasco R.A., Dias F.C.F., et al. Mechanism of LH release after peripheral administration of kisspeptin in cattle // PLoS One. 2022. Vol. 17, N 12. P. e0278564. doi: 10.1371/journal.pone.0278564

[51] Lents CA. Review: kisspeptin and reproduction in the pig. Animal. 2019;13(12):2986–2999. doi: 10.1017/S1751731119001666

[52] Lents C.A. Review: kisspeptin and reproduction in the pig // Animal. 2019. Vol. 13, N 12. P. 2986–2999. doi: 10.1017/S1751731119001666

RIGHTS & PERMISSIONS

Eco-Vector