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

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

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.

Full Text

Restricted Access

About the authors

Alina A. Nuzhnova

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: lin.panaiotis@yandex.ru
ORCID iD: 0009-0002-1607-1471

Junior Research Associate

Russian Federation, Saint Petersburg

Marina I. Kostina

Peter the Great Saint Petersburg Polytechnic University

Email: koctena@list.ru
ORCID iD: 0009-0005-1060-5489

student

Russian Federation, Saint Petersburg

Aleksandra A. Blazhenko

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott; Institute of Experimental Medicine

Author for correspondence.
Email: alexandrablazhenko@jmail.com
ORCID iD: 0000-0002-8079-0991
SPIN-code: 8762-3604

Research Associate, Junior Research Associate at the S.V. Anichkov Department of Neuropharmacology

Russian Federation, Saint Petersburg; Saint Petersburg

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. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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.
  14. 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.)
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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
  21. 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
  22. 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
  23. 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
  24. 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
  25. 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
  26. Lents CA. Review: kisspeptin and reproduction in the pig. Animal. 2019;13(12):2986–2999. doi: 10.1017/S1751731119001666

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Concentration of luteinizing hormone (LH) depending on the concentration of injected synthetic analog of kisspeptin 1 and time of exposure. The data is presented as the mean and standard deviation. ** p < 0,001; **** p < 0,0001

Download (76KB)
Indexing metadata
3. Fig. 2. Сoncentration of gonadal luteinizing hormone (LH) as depending on kisspeptin 1 concentration without regard to resting time. The data is presented as the mean and standard deviation. ***p = 0,0001; ****p < 0,0001

Download (60KB)
Indexing metadata
4. Fig. 3. Concentration of follicle-stimulating hormone (FSH) depending on the concentration of injected synthetic analog of kisspeptin 1 and time of exposure. The data is presented as median and Q3. * p < 0,05; ** p < 0,001; *** p = 0,0001; **** p < 0,0001

Download (78KB)
Indexing metadata
5. Fig. 4. Сoncentration of follicle-stimulating hormone (FSH) as depending on kisspeptin 1 concentration without regard to resting time. The data is presented as median and Q3. *** p = 0,0001

Download (58KB)
Indexing metadata

Copyright (c) 2024 Eco-Vector


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 74760 от 29.12.2018 г.