Cell and Tissue Research

, Volume 379, Issue 2, pp 349–372 | Cite as

Distribution of Kiss2 receptor in the brain and its localization in neuroendocrine cells in the zebrafish

  • Satoshi Ogawa
  • Mageswary Sivalingam
  • Rachel Anthonysamy
  • Ishwar S. ParharEmail author
Regular Article


Kisspeptin is a hypothalamic neuropeptide, which acts directly on gonadotropin-releasing hormone (GnRH)-secreting neurons via its cognate receptor (GPR54 or Kiss-R) to stimulate GnRH secretion in mammals. In non-mammalian vertebrates, there are multiple kisspeptins (Kiss1 and Kiss2) and Kiss-R types. Recent gene knockout studies have demonstrated that fish kisspeptin systems are not essential in the regulation of reproduction. Studying the detailed distribution of kisspeptin receptor in the brain and pituitary is important for understanding the multiple action sites and potential functions of the kisspeptin system. In the present study, we generated a specific antibody against zebrafish Kiss2-R (=Kiss1Ra/GPR54-1/Kiss-R2/KissR3) and examined its distribution in the brain and pituitary. Kiss2-R-immunoreactive cell bodies are widely distributed in the brain including in the dorsal telencephalon, preoptic area, hypothalamus, optic tectum, and in the hindbrain regions. Double-labeling showed that not all but a subset of preoptic GnRH3 neurons expresses Kiss2-R, while Kiss2-R is expressed in most of the olfactory GnRH3 neurons. In the posterior preoptic region, Kiss2-R immunoreactivity was seen in vasotocin cells. In the pituitary, Kiss2-R immunoreactivity was seen in corticotropes, but not in gonadotropes. The results in this study suggest that Kiss2 and Kiss2-R signaling directly serve non-reproductive functions and indirectly subserve reproductive functions in teleosts.


Kisspeptin GnRH GPR54 Reproduction Teleost 


Author contributions

SO and ISP designed research; SO and ISP created antiserum for zebrafish Kiss2 receptor; MS and RA performed and analyzed the ISH and ICC experiments; MS performed Western blot analysis; MS and SO analyzed the data; and SO, MS, and ISP wrote the paper.


This work was supported by grants from the Malaysian Ministry of Higher Education, FRGS/2/2010/ST/MUSM/03/2, FRGS/1/2014/ST03/MUSM/02/1 (to S.O.), FRGS/1/2016/STG03/MUSM/01/1 (to I.S.P) and Monash University Malaysia, SO-10-01 (to S.O.), IP-09-01 (to I.S.P).

Compliance with ethical statements

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All experimental procedures were performed under the guidelines of the Animal Ethics Committee of Monash University (approval number: MARP/2012/120).

Supplementary material

441_2019_3089_Fig12_ESM.png (1.6 mb)
Supplementary Figure 1.

Photomicrographs of immunoreactivity of the mouse anti-human POMC antibody (POMC-Ab, A) and DIG-in situ hybridization of pomc mRNA (B) in the pituitary of zebrafish. In the RPD region, very weak POMC-immunoreactivity were observed (arrows). Scale bars: 100 μm (PNG 1606 kb)

441_2019_3089_MOESM1_ESM.tif (16.6 mb)
High resolution image (TIF 17026 kb)


  1. Abe H, Oka Y (2006) Neuromodulatory functions of terminal nerve-GnRH neurons. Fish Physiology 25:455–503Google Scholar
  2. Abraham E, Palevitch O, Gothilf Y, Zohar Y (2010) Targeted gonadotropin-releasing hormone-3 neuron ablation in zebrafish: effects on neurogenesis, neuronal migration, and reproduction. Endocrinology 151:332–340PubMedGoogle Scholar
  3. Abraham E, Palevitch O, Ijiri S, Du SJ, Gothilf Y, Zohar Y (2008) Early development of forebrain gonadotrophin-releasing hormone (GnRH) neurones and the role of GnRH as an autocrine migration factor. J Neuroendocrinol 20:394–405PubMedGoogle Scholar
  4. Agetsuma M, Aizawa H, Aoki T, Nakayama R, Takahoko M, Goto M, Sassa T, Amo R, Shiraki T, Kawakami K, Hosoya T, Higashijima S, Okamoto H (2010) The habenula is crucial for experience-dependent modification of fear responses in zebrafish. Nat Neurosci 13:1354–1356PubMedGoogle Scholar
  5. Backholer K, Smith JT, Rao A, Pereira A, Iqbal J, Ogawa S, Li Q, Clarke IJ (2010) Kisspeptin cells in the ewe brain respond to leptin and communicate with neuropeptide Y and proopiomelanocortin cells. Endocrinology 151:2233–2243PubMedGoogle Scholar
  6. Bae Y-K, Kani S, Shimizu T, Tanabe K, Nojima H, Kimura Y, Higashijima S-I, Hibi M (2009) Anatomy of zebrafish cerebellum and screen for mutations affecting its development. Dev Biol 330:406–426PubMedGoogle Scholar
  7. Beck BH, Fuller SA, Peatman E, McEntire ME, Darwish A, Freeman DW (2012) Chronic exogenous kisspeptin administration accelerates gonadal development in basses of the genus Morone. Comp Biochem Physiol A Mol Integr Physiol 162:265–273PubMedGoogle Scholar
  8. Chang JP, Mar A, Wlasichuk M, Wong AOL (2012) Kisspeptin-1 directly stimulates LH and GH secretion from goldfish pituitary cells in a Ca2+-dependent manner. Gen Comp Endocrinol 179:38–46PubMedGoogle Scholar
  9. Comninos AN, Anastasovska J, Sahuri-Arisoylu M, Li X, Li S, Hu M, Jayasena CN, Ghatei MA, Bloom SR, Matthews PM (2016) Kisspeptin signaling in the amygdala modulates reproductive hormone secretion. Brain Struct Funct 221:2035–2047PubMedGoogle Scholar
  10. Comninos AN, Dhillo WS (2018) Emerging roles of kisspeptin in sexual and emotional brain processing. Neuroendocrinology 106:195–202PubMedGoogle Scholar
  11. D’Anglemont de Tassigny X, Fagg LA, Carlton MBL, Colledge WH (2008) Kisspeptin can stimulate gonadotropin-releasing hormone (GnRH) release by a direct action at GnRH nerve terminals. Endocrinology 149:3926–3932PubMedPubMedCentralGoogle Scholar
  12. Delgado L, Schmachtenberg O (2008) Immunohistochemical localization of GABA, GAD65, and the receptor subunits GABA Aα1 and GABA B1 in the zebrafish cerebellum. Cerebellum 7:444–450PubMedGoogle Scholar
  13. Dungan HM, Clifton DK, Steiner RA (2006) Minireview: kisspeptin neurons as central processors in the regulation of gonadotropin-releasing hormone secretion. Endocrinology 147:1154–1158PubMedGoogle Scholar
  14. Escobar S, Servili A, Espigares F, Gueguen M-M, Brocal I, Felip A, Gómez A, Carrillo M, Zanuy S, Kah O (2013) Expression of kisspeptins and kiss receptors suggests a large range of functions for kisspeptin systems in the brain of the European sea bass. PLoS One 8:e70177PubMedPubMedCentralGoogle Scholar
  15. Espigares F, Zanuy S, Gómez A (2015) Kiss2 as a regulator of Lh and Fsh secretion via paracrine/autocrine signaling in the teleost fish European sea bass (Dicentrarchus labrax). Biol Reprod 93:1–12Google Scholar
  16. Felip A, Zanuy S, Pineda R, Pinilla L, Carrillo M, Tena-Sempere M, Gomez A (2009) Evidence for two distinct KiSS genes in non-placental vertebrates that encode kisspeptins with different gonadotropin-releasing activities in fish and mammals. Mol Cell Endocrinol 312:61–71PubMedGoogle Scholar
  17. Freeman WJ (2005) NDN, volume transmission, and self-organization in brain dynamics. J Integr Neurosci 4:407–421PubMedGoogle Scholar
  18. Fu L-Y, van den Pol AN (2010) Kisspeptin directly excites anorexigenic proopiomelanocortin neurons but inhibits orexigenic neuropeptide Y cells by an indirect synaptic mechanism. J Neurosci 30:10205–10219PubMedPubMedCentralGoogle Scholar
  19. Gopinath A, Andrew TL, Whitlock KE (2004) Temporal and spatial expression of gonadotropin releasing hormone (GnRH) in the brain of developing zebrafish (Danio rerio). Gene Expr Patterns 4:65–70PubMedGoogle Scholar
  20. Gopurappilly R, Ogawa S, Parhar IS (2013) Functional significance of GnRH and kisspeptin, and their cognate receptors in teleost reproduction. Front Endocrinol 4:24Google Scholar
  21. Grone BP, Maruska KP, Korzan WJ, Fernald RD (2010) Social status regulates kisspeptin receptor mRNA in the brain of Astatotilapia burtoni. Gen Comp Endocrinol 169:98–107PubMedPubMedCentralGoogle Scholar
  22. Herbison AE, D’Anglemont de Tassigny X, Doran J, Colledge WH (2010) Distribution and postnatal development of Gpr54 gene expression in mouse brain and gonadotropin-releasing hormone neurons. Endocrinology 151:312–321PubMedGoogle Scholar
  23. Herkenham M (1987) Mismatches between neurotransmitter and receptor localizations in brain: observations and implications. Neuroscience 23:1–38PubMedGoogle Scholar
  24. Higo S, Honda S, Iijima N, Ozawa H (2016) Mapping of kisspeptin receptor mRNA in the whole rat brain and its co-localisation with oxytocin in the paraventricular nucleus. J Neuroendocrinol 28Google Scholar
  25. Kanda S, Akazome Y, Matsunaga T, Yamamoto N, Yamada S, Tsukamura H, Maeda K, Oka Y (2008) Identification of KiSS-1 product kisspeptin and steroid-sensitive sexually dimorphic kisspeptin neurons in medaka (Oryzias latipes). Endocrinology 149:2467–2476PubMedGoogle Scholar
  26. Kanda S, Akazome Y, Mitani Y, Okubo K, Oka Y (2013) Neuroanatomical evidence that kisspeptin directly regulates isotocin and vasotocin neurons. PLoS One 8:e62776PubMedPubMedCentralGoogle Scholar
  27. Keen KL, Wegner FH, Bloom SR, Ghatei MA, Terasawa E (2008) An increase in kisspeptin-54 release occurs with the pubertal increase in luteinizing hormone-releasing hormone-1 release in the stalk-median eminence of female rhesus monkeys in vivo. Endocrinology 149:4151–4157PubMedPubMedCentralGoogle Scholar
  28. Kim NN, Choi Y-U, Park H-S, Choi CY (2015) Kisspeptin regulates the somatic growth-related factors of the cinnamon clownfish Amphiprion melanopus. Comp Biochem Physiol A Mol Integr Physiol 179:17–24PubMedGoogle Scholar
  29. Kitahashi T, Ogawa S, Parhar IS (2009) Cloning and expression of kiss2 in the zebrafish and medaka. Endocrinology 150:821–831PubMedGoogle Scholar
  30. Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden J, Le Poul E, Brezillon S, Tyldesley R, Suarez-Huerta N, Vandeput F (2001) The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem 276:34631–34636PubMedGoogle Scholar
  31. Lal P, Tanabe H, Suster ML, Ailani D, Kotani Y, Muto A, Itoh M, Iwasaki M, Wada H, Yaksi E (2018) Identification of a neuronal population in the telencephalon essential for fear conditioning in zebrafish. BMC Biol 16:45PubMedPubMedCentralGoogle Scholar
  32. Larson E, O'Malley D, Melloni R (2006) Aggression and vasotocin are associated with dominant-subordinate relationships in zebrafish. Behav Brain Res 167:94–102PubMedGoogle Scholar
  33. Lee A, Mathuru AS, Teh C, Kibat C, Korzh V, Penney TB, Jesuthasan S (2010) The habenula prevents helpless behavior in larval zebrafish. Curr Biol 20:2211–2216PubMedGoogle Scholar
  34. Lee YR, Tsunekawa K, Moon MJ, Um HN, Hwang JI, Osugi T, Otaki N, Sunakawa Y, Kim K, Vaudry H, Kwon HB, Seong JY, Tsutsui K (2009) Molecular evolution of multiple forms of kisspeptins and GPR54 receptors in vertebrates. Endocrinology 150:2837–2846PubMedGoogle Scholar
  35. Li S, Zhang Y, Liu Y, Huang X, Huang W, Lu D, Zhu P, Shi Y, Cheng CH, Liu X, Lin H (2009) Structural and functional multiplicity of the kisspeptin/GPR54 system in goldfish (Carassius auratus). J Endocrinol 201:407–418PubMedGoogle Scholar
  36. Liu N-A, Huang H, Yang Z, Herzog W, Hammerschmidt M, Lin S, Melmed S (2003) Pituitary corticotroph ontogeny and regulation in transgenic zebrafish. Mol Endocrinol 17:959–966PubMedGoogle Scholar
  37. Liu Q, Bhattarai S, Wang N, Sochacka-Marlowe A (2015) Differential expression of protocadherin-19, protocadherin-17, and cadherin-6 in adult zebrafish brain. J Comp Neurol 523:1419–1442PubMedPubMedCentralGoogle Scholar
  38. Liu Y, Tang H, Xie R, Li S, Liu X, Lin H, Zhang Y, Cheng CH (2017) Genetic evidence for multifactorial control of the reproductive axis in zebrafish. Endocrinology 158:604–611PubMedGoogle Scholar
  39. Luque RM, Córdoba-Chacón J, Gahete MD, Navarro VM, Tena-Sempere M, Kineman RD, Castaño JP (2011) Kisspeptin regulates gonadotroph and somatotroph function in nonhuman primate pituitary via common and distinct signaling mechanisms. Endocrinology 152:957–966PubMedPubMedCentralGoogle Scholar
  40. Martel J-C, St-Pierre S, Quirion R (1986) Neuropeptide Y receptors in rat brain: autoradiographic localization. Peptides 7:55–60PubMedGoogle Scholar
  41. Marvel M, Spicer OS, Wong T-T, Zmora N, Zohar Y (2018) Knockout of the Gnrh genes in zebrafish: effects on reproduction and potential compensation by reproductive and feeding-related neuropeptides. Biol Reprod 99:565–577PubMedGoogle Scholar
  42. Mechaly AS, Tovar-Bohórquez M, Mechaly AE, Suku E, Giorgetti A, Pérez M, Ortí G, Viñas J, Somoza GM (2018) Evidences of alternative splicing as a regulatory mechanism for Kissr2 in pejerrey fish. Front Endocrinol 9:604Google Scholar
  43. Meek J (1983) Functional anatomy of the tectum mesencephali of the goldfish. An explorative analysis of the functional implications of the laminar structural organization of the tectum. Brain Res Rev 6:247–297Google Scholar
  44. Mitani Y, Kanda S, Akazome Y, Zempo B, Oka Y (2010) Hypothalamic Kiss1 but not Kiss2 neurons are involved in estrogen feedback in medaka (Oryzias latipes). Endocrinology 151:1751–1759PubMedGoogle Scholar
  45. Mueller T, Dong Z, Berberoglu MA, Guo S (2011) The dorsal pallium in zebrafish, Danio rerio (Cyprinidae, Teleostei). Brain Res 1381:95–105PubMedPubMedCentralGoogle Scholar
  46. Mueller T, Guo S (2009) The distribution of GAD67-mRNA in the adult zebrafish (teleost) forebrain reveals a prosomeric pattern and suggests previously unidentified homologies to tetrapods. J Comp Neurol 516:553–568PubMedPubMedCentralGoogle Scholar
  47. Mueller T, Vernier P, Wullimann MF (2004) The adult central nervous cholinergic system of a neurogenetic model animal, the zebrafish Danio rerio. Brain Res 1011:156–169PubMedGoogle Scholar
  48. Nakajo M, Kanda S, Karigo T, Takahashi A, Akazome Y, Uenoyama Y, Kobayashi M, Oka Y (2018) Evolutionally conserved function of kisspeptin neuronal system is nonreproductive regulation as revealed by nonmammalian study. Endocrinology 159:163–183PubMedGoogle Scholar
  49. Nathan FM, Ogawa S, Parhar IS (2015) Neuronal connectivity between habenular glutamate-kisspeptin1 co-expressing neurons and the raphe 5-HT system. J Neurochem 135:814–829PubMedPubMedCentralGoogle Scholar
  50. Nocillado J, Biran J, Lee Y, Levavi-Sivan B, Mechaly AS, Zohar Y, Elizur A (2012) The Kiss2 receptor (Kiss2r) gene in Southern Bluefin Tuna, Thunnus maccoyii and in Yellowtail Kingfish, Seriola lalandi–functional analysis and isolation of transcript variants. Mol Cell Endocrinol 362:211–220PubMedGoogle Scholar
  51. Oehlmann VD, Korte H, Sterner C, Korsching SI (2002) A neuropeptide FF-related gene is expressed selectively in neurons of the terminal nerve in Danio rerio. Mech Dev 117:357–361PubMedGoogle Scholar
  52. Ogawa S, Akiyama G, Kato S, Soga T, Sakuma Y, Parhar IS (2006) Immunoneutralization of gonadotropin-releasing hormone type-III suppresses male reproductive behavior of cichlids. Neurosci Lett 403:201–205PubMedGoogle Scholar
  53. Ogawa S, Nathan FM, Parhar IS (2014) Habenular kisspeptin modulates fear in the zebrafish. Proc Natl Acad Sci U S A 111:3841–3846PubMedPubMedCentralGoogle Scholar
  54. Ogawa S, Ng KW, Ramadasan PN, Nathan FM, Parhar IS (2012) Habenular Kiss1 neurons modulate the serotonergic system in the brain of zebrafish. Endocrinology 153:2398–2407PubMedGoogle Scholar
  55. Ogawa S, Ng KW, Xue X, Ramadasan PN, Sivalingam M, Li S, Levavi-Sivan B, Lin H, Liu X, Parhar IS (2013) Thyroid hormone upregulates hypothalamic kiss2 gene in the male Nile tilapia, Oreochromis niloticus. Front Endocrinol 4:184Google Scholar
  56. Ogawa S, Parhar IS (2013) Anatomy of the kisspeptin systems in teleosts. Gen Comp Endocrinol 181:169–174PubMedGoogle Scholar
  57. Ogawa S, Parhar IS (2018) Biological significance of kisspeptin–kiss 1 receptor signaling in the habenula of teleost species. Front Endocrinol 9:222Google Scholar
  58. Ogawa S, Sivalingam M, Biran J, Golan M, Anthonysamy RS, Levavi-Sivan B, Parhar IS (2016) Distribution of LPXRFa, a gonadotropin-inhibitory hormone ortholog peptide, and LPXRFa receptor in the brain and pituitary of the tilapia. J Comp Neurol 524:2753–2775PubMedGoogle Scholar
  59. Ohga H, Selvaraj S, Adachi H, Imanaga Y, Nyuji M, Yamaguchi A, Matsuyama M (2014) Functional analysis of kisspeptin peptides in adult immature chub mackerel (Scomber japonicus) using an intracerebroventricular administration method. Neurosci Lett 561:203–207PubMedGoogle Scholar
  60. Oka Y (2009) Three types of gonadotrophin-releasing hormone neurones and steroid-sensitive sexually dimorphic kisspeptin neurones in teleosts. J Neuroendocrinol 21:334–338PubMedGoogle Scholar
  61. Parhar I, Ogawa S, Kitahashi T (2012) RFamide peptides as mediators in environmental control of GnRH neurons. Prog Neurobiol 98:176–196PubMedGoogle Scholar
  62. Parhar IS (2002) Cell migration and evolutionary significance of GnRH subtypes. Prog Brain Res 141:3–17PubMedGoogle Scholar
  63. Parhar IS, Ogawa S, Sakuma Y (2004) Laser-captured single digoxigenin-labeled neurons of gonadotropin-releasing hormone types reveal a novel G protein-coupled receptor (Gpr54) during maturation in cichlid fish. Endocrinology 145:3613–3618PubMedGoogle Scholar
  64. Park MK, Wakabayashi K (1986) Preparation of a monoclonal antibody to common amino acid sequence of LHRH and its application. Endocrinol Jpn 33:257–272PubMedGoogle Scholar
  65. Pasquier J, Kamech N, Lafont A-G, Vaudry H, Rousseau K, Dufour S (2014) Molecular evolution of GPCRs: Kisspeptin/kisspeptin receptors. J Mol Endocrinol 52:T101–T117PubMedGoogle Scholar
  66. Pasquier J, Lafont AG, Leprince J, Vaudry H, Rousseau K, Dufour S (2011) First evidence for a direct inhibitory effect of kisspeptins on LH expression in the eel, Anguilla anguilla. Gen Comp Endocrinol 173:216–225PubMedGoogle Scholar
  67. Pert CB, Ruff MR, Weber RJ, Herkenham M (1985) Neuropeptides and their receptors: a psychosomatic network. J Immunol 135:820S–826SPubMedGoogle Scholar
  68. Peter RE, Yu KL, Marchant TA, Rosenblum PM (1990) Direct neural regulation of the teleost adenohypophysis. J Exp Zool 256:84–89Google Scholar
  69. Ramakrishnan S, Lee W, Navarre S, Kozlowski DJ, Wayne NL (2010) Acquisition of spontaneous electrical activity during embryonic development of gonadotropin-releasing hormone-3 neurons located in the terminal nerve of transgenic zebrafish (Danio rerio). Gen Comp Endocrinol 168:401–407PubMedPubMedCentralGoogle Scholar
  70. Ramaswamy S, Guerriero KA, Gibbs RB, Plant TM (2008) Structural interactions between kisspeptin and GnRH neurons in the mediobasal hypothalamus of the male rhesus monkey (Macaca mulatta) as revealed by double immunofluorescence and confocal microscopy. Endocrinology 149:4387–4395PubMedPubMedCentralGoogle Scholar
  71. Rao YS, Mott NN, Pak TR (2011) Effects of kisspeptin on parameters of the HPA axis. Endocrine 39:220–228PubMedGoogle Scholar
  72. Rink E, Wullimann MF (2001) The teleostean (zebrafish) dopaminergic system ascending to the subpallium (striatum) is located in the basal diencephalon (posterior tuberculum). Brain Res 889:316–330PubMedGoogle Scholar
  73. Selvaraj S, Ohga H, Kitano H, Nyuji M, Yamaguchi A, Matsuyama M (2013) Peripheral administration of Kiss1 pentadecapeptide induces gonadal development in sexually immature adult scombroid fish. Zool Sci 30:446–454PubMedGoogle Scholar
  74. Semsar K, Kandel F, Godwin J (2001) Manipulations of the AVT system shift social status and related courtship and aggressive behaviour in the bluehead wrasse. Horm Behav 40:21–31PubMedGoogle Scholar
  75. Servili A, Le Page Y, Leprince J, Caraty A, Escobar S, Parhar IS, Seong JY, Vaudry H, Kah O (2011) Organization of two independent kisspeptin systems derived from evolutionary-ancient kiss genes in the brain of zebrafish. Endocrinology 152:1527–1540PubMedGoogle Scholar
  76. Shahjahan M, Motohashi E, Doi H, Ando H (2010) Elevation of Kiss2 and its receptor gene expression in the brain and pituitary of grass puffer during the spawning season. Gen Comp Endocrinol 169:48–57PubMedGoogle Scholar
  77. Soga T, Ogawa S, Millar RP, Sakuma Y, Parhar IS (2005) Localization of the three GnRH types and GnRH receptors in the brain of a cichlid fish: insights into their neuroendocrine and neuromodulator functions. J Comp Neurol 487:28–41PubMedGoogle Scholar
  78. Song Y, Duan X, Chen J, Huang W, Zhu Z, Hu W (2015) The distribution of kisspeptin (Kiss)1- and Kiss2-positive neurones and their connections with gonadotrophin-releasing hormone-3 neurones in the zebrafish brain. J Neuroendocrinol 27:198–211PubMedGoogle Scholar
  79. Spicer OS, Wong T-T, Zmora N, Zohar Y (2016) Targeted mutagenesis of the hypophysiotropic Gnrh3 in zebrafish (Danio rerio) reveals no effects on reproductive performance. PLoS One 11:e0158141PubMedPubMedCentralGoogle Scholar
  80. Steven C, Lehnen N, Kight K, Ijiri S, Klenke U, Harris WA, Zohar Y (2003) Molecular characterization of the GnRH system in zebrafish (Danio rerio): cloning of chicken GnRH-II, adult brain expression patterns and pituitary content of salmon GnRH and chicken GnRH-II. Gen Comp Endocrinol 133:27–37PubMedGoogle Scholar
  81. Takahashi A, Kanda S, Abe T, Oka Y (2016) Evolution of the hypothalamic-pituitary-gonadal axis regulation in vertebrates revealed by knockout medaka. Endocrinology 157:3994–4002PubMedGoogle Scholar
  82. Tang H, Liu Y, Luo D, Ogawa S, Yin Y, Li S, Zhang Y, Hu W, Parhar IS, Lin H, Liu X, Cheng CHK (2015) The kiss/kissr systems are dispensable for zebrafish reproduction: evidence from gene knockout studies. Endocrinology 156:589–599PubMedGoogle Scholar
  83. Thompson RR, Walton JC (2004) Peptide effects on social behavior: effects of vasotocin and isotocin on social approach behavior in male goldfish (Carassius auratus). Behav Neurosci 118:620PubMedGoogle Scholar
  84. Trudeau VL (2018) Facing the challenges of neuropeptide gene knockouts: why do they not inhibit reproduction in adult teleost fish? Front Neurosci 12:302PubMedPubMedCentralGoogle Scholar
  85. van Aerle R, Kille P, Lange A, Tyler CR (2008) Evidence for the existence of a functional Kiss1/Kiss1 receptor pathway in fish. Peptides 29:57–64PubMedGoogle Scholar
  86. Van Pett K, Viau V, Bittencourt JC, Chan RK, Li HY, Arias C, Prins GS, Perrin M, Vale W, Sawchenko PE (2000) Distribution of mRNAs encoding CRF receptors in brain and pituitary of rat and mouse. J Comp Neurol 428:191–212PubMedGoogle Scholar
  87. van den Pol AN (2012) Neuropeptide transmission in brain circuits. Neuron 76:98–115PubMedPubMedCentralGoogle Scholar
  88. Wang B, Yang G, Liu Q, Qin J, Xu Y, Li W, Liu X, Shi B (2017) Inhibitory action of tongue sole LPXRFa, the piscine ortholog of gonadotropin-inhibitory hormone, on the signaling pathway induced by tongue sole kisspeptin in COS-7 cells transfected with their cognate receptors. Peptides 95:62–67PubMedGoogle Scholar
  89. Wang B, Yang G, Xu Y, Li W, Liu X (2019) Recent studies of LPXRFa receptor signaling in fish and other vertebrates. Gen Comp Endocrinol 277:3–8PubMedGoogle Scholar
  90. Wang Q, Sham KWY, Ogawa S, Li S, Parhar IS, Cheng CHK, Liu X, Lin H (2013) Regulation of the two kiss promoters in goldfish (Carassius auratus) by estrogen via different ERα pathways. Mol Cell Endocrinol 375:130–139PubMedGoogle Scholar
  91. Whitlock KE, Smith KM, Kim H, Harden MV (2005) A role for foxd3 and sox10 in the differentiation of gonadotropin-releasing hormone (GnRH) cells in the zebrafish Danio rerio. Development 132:5491–5502PubMedGoogle Scholar
  92. Wullimann MF, Rupp B, Reichert H (1996) Neuroanatomy of the zebrafish brain: a topologocal atlas. Birkhauser, BerlinGoogle Scholar
  93. Xia W, Smith O, Zmora N, Xu S, Zohar Y (2014) Comprehensive analysis of GnRH2 neuronal projections in zebrafish. Sci Rep 4:3676PubMedPubMedCentralGoogle Scholar
  94. Yamamoto N, Oka Y, Kawashima S (1997) Lesions of gonadotropin-releasing hormone-immunoreactive terminal nerve cells: effects on the reproductive behavior of male dwarf gouramis. Neuroendocrinology 65:403–412PubMedGoogle Scholar
  95. Yang B, Jiang Q, Chan T, Ko WK, Wong AO (2010) Goldfish kisspeptin: molecular cloning, tissue distribution of transcript expression, and stimulatory effects on prolactin, growth hormone and luteinizing hormone secretion and gene expression via direct actions at the pituitary level. Gen Comp Endocrinol 165:60–71PubMedGoogle Scholar
  96. Zhang Y, Li S, Liu Y, Lu D, Chen H, Huang X, Liu X, Meng Z, Lin H, Cheng CHK (2010) Structural diversity of the GnIH/GnIH receptor system in teleost: its involvement in early development and the negative control of LH release. Peptides 31:1034–1043PubMedGoogle Scholar
  97. Zhao Y, Lin M-CA, Mock A, Yang M, Wayne NL (2014) Kisspeptins modulate the biology of multiple populations of gonadotropin-releasing hormone neurons during embryogenesis and adulthood in zebrafish (Danio rerio). PLoS One 9:e104330PubMedPubMedCentralGoogle Scholar
  98. Zmora N, Stubblefield J, Golan M, Servili A, Levavi-Sivan B, Zohar Y (2014) The medio-basal hypothalamus as a dynamic and plastic reproduction-related kisspeptin-gnrh-pituitary center in fish. Endocrinology 155:1874–1886PubMedGoogle Scholar
  99. Zmora N, Stubblefield J, Zulperi Z, Biran J, Levavi-Sivan B, Muñoz-Cueto J-A, Zohar Y (2012) Differential and gonad stage-dependent roles of kisspeptin1 and kisspeptin2 in reproduction in the modern teleosts, Morone species. Biol Reprod 86:177Google Scholar
  100. Zmora N, Stubblefield JD, Wong T-T, Levavi-Sivan B, Millar RP, Zohar Y (2015) Kisspeptin antagonists reveal kisspeptin 1 and kisspeptin 2 differential regulation of reproduction in the teleost, Morone saxatilis. Biol Reprod 93(76):71–12Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Satoshi Ogawa
    • 1
  • Mageswary Sivalingam
    • 1
  • Rachel Anthonysamy
    • 1
  • Ishwar S. Parhar
    • 1
    Email author
  1. 1.Brain Research Institute, Jeffrey Cheah School of Medicine and Health SciencesMonash University MalaysiaBandar SunwayMalaysia

Personalised recommendations