Distribution of Kiss2 receptor in the brain and its localization in neuroendocrine cells in the zebrafish
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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.
KeywordsKisspeptin GnRH GPR54 Reproduction Teleost
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.
All experimental procedures were performed under the guidelines of the Animal Ethics Committee of Monash University (approval number: MARP/2012/120).
- Abe H, Oka Y (2006) Neuromodulatory functions of terminal nerve-GnRH neurons. Fish Physiology 25:455–503Google Scholar
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Ogawa S, Parhar IS (2018) Biological significance of kisspeptin–kiss 1 receptor signaling in the habenula of teleost species. Front Endocrinol 9:222Google Scholar
- Peter RE, Yu KL, Marchant TA, Rosenblum PM (1990) Direct neural regulation of the teleost adenohypophysis. J Exp Zool 256:84–89Google Scholar
- 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
- 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
- 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
- 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
- Wullimann MF, Rupp B, Reichert H (1996) Neuroanatomy of the zebrafish brain: a topologocal atlas. Birkhauser, BerlinGoogle Scholar
- 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
- 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
- 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