Skip to main content

Structure, Synthesis, and Phylogeny of Kisspeptin and its Receptor

  • Chapter
  • First Online:
Kisspeptin Signaling in Reproductive Biology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 784))

Abstract

The kisspeptin system is considered to be essential for successful mammalian reproduction. In addition to the Kiss1 peptide, Kiss2, the product of kiss2 (the kiss1 paralogue), has also been shown to activate kisspeptin receptor signaling pathways in nonmammalian species. Furthermore, in nonmammalian species, there are two subtypes of receptors, Gpr54-1 (known as GPR54 or Kiss1R in mammals) and Gpr54-2. Although complete understanding of the two kisspeptin—two kisspeptin receptor systems in vertebrates is not so simple, a careful examination of the phylogeny of their genes may provide insights into the functional generality and differences among the kisspeptin systems in different animal phyla. In this chapter, we first discuss the structure of kisspeptin ligands, Kiss1 and Kiss2, and their characteristics as physiologically active peptides. Then, we discuss the evolutionary traits of kiss1 and kiss2 genes and their receptor genes, gpr54-1 and gpr54-2. It appears that each animal species has selected either kiss1 or kiss2 rather randomly, leading us to propose that some of the important characteristics of kisspeptin neurons, such as steroid sensitivity and the anatomical relationship with the hypophysiotropic GnRH1 neurons, may be the keys to understanding the general functions of different kisspeptin neuronal populations throughout vertebrates. Species differences in kiss1/kiss2 may also provide insights into the evolutionary mechanisms of paralogous gene-expressing neuronal systems. Finally, because kisspeptins belong to one of the members of the RFamide peptide families, we discuss the functional divergence of kisspeptins from the other RFamide peptides, which may be explained from phylogenetic viewpoints.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Notes

  1. 1.

    According to the Zebrafish Information Network, ZFIN; http://zfin.org/zfinfo/nomen.html, we will italicize gene names, such as kiss1 and kiss2, and romanize protein and peptide name, such as Kiss1 and Kiss2 in this chapter. We will call the receptor for kisspeptins as “GPR54” because of the promiscuous nature of ligands and receptors for RF amide families, including kisspeptin. For details, see Kanda and Oka [37].

  2. 2.

    In the vertebrate lineage, whole genome duplication (WGD) events [8] are considered to have taken place three times in teleosts (1R-3R) and twice (1R and 2R) in tetrapods [9].

References

  1. Ohtaki T, Shintani Y, Honda S, Matsumoto H, Hori A et al (2001) Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature 411:613–617

    Article  PubMed  CAS  Google Scholar 

  2. Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM et al (2001) The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem 276:34631–34636

    Article  PubMed  CAS  Google Scholar 

  3. Lee YR, Tsunekawa K, Moon MJ, Um HN, Hwang JI et al (2009) Molecular evolution of multiple forms of kisspeptins and GPR54 receptors in vertebrates. Endocrinology 150:2837–2846

    Article  PubMed  CAS  Google Scholar 

  4. Moon JS, Lee YR, Oh DY, Hwang JI, Lee JY et al (2009) Molecular cloning of the bullfrog kisspeptin receptor GPR54 with high sensitivity to Xenopus kisspeptin. Peptides 30:171–179

    Article  PubMed  CAS  Google Scholar 

  5. Li S, Zhang Y, Liu Y, Huang X, Huang W et al (2009) Structural and functional multiplicity of the kisspeptin/GPR54 system in goldfish (Carassius auratus). J Endocrinol 201:407–418

    Article  PubMed  CAS  Google Scholar 

  6. Felip A, Zanuy S, Pineda R, Pinilla L, Carrillo M et al (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 312:61–71

    Article  PubMed  CAS  Google Scholar 

  7. Um HN, Han JM, Hwang JI, Hong SI, Vaudry H et al (2010) Molecular coevolution of kisspeptins and their receptors from fish to mammals. Ann N Y Acad Sci 1200:67–74

    Article  PubMed  CAS  Google Scholar 

  8. Kim DK, Cho EB, Moon MJ, Park S, Hwang JI et al (2012) Molecular coevolution of neuropeptides gonadotropin-releasing hormone and kisspeptin with their cognate G protein-coupled receptors. Front Neurosci 6:3

    PubMed  Google Scholar 

  9. Gottsch ML, Clifton DK, Steiner RA (2009) From KISS1 to kisspeptins: An historical ­perspective and suggested nomenclature. Peptides 30(1): 4–9

    PubMed  Google Scholar 

  10. Dumalska I, Wu M, Morozova E, Liu R, van den Pol A et al (2008) Excitatory effects of the puberty-initiating peptide kisspeptin and group I metabotropic glutamate receptor agonists differentiate two distinct subpopulations of gonadotropin-releasing hormone neurons. J Neurosci 28:8003–8013

    Article  PubMed  CAS  Google Scholar 

  11. Han SK, Gottsch ML, Lee KJ, Popa SM, Smith JT et al (2005) Activation of gonadotropin-­releasing hormone neurons by kisspeptin as a neuroendocrine switch for the onset of puberty. J Neurosci 25:11349–11356

    Article  PubMed  CAS  Google Scholar 

  12. Liu X, Lee K, Herbison AE (2008) Kisspeptin excites gonadotropin-releasing hormone neurons through a phospholipase C/calcium-dependent pathway regulating multiple ion channels. Endocrinology 149:4605–4614

    Article  PubMed  CAS  Google Scholar 

  13. Pielecka-Fortuna J, Chu Z, Moenter SM (2008) Kisspeptin acts directly and indirectly to increase gonadotropin-releasing hormone neuron activity and its effects are modulated by estradiol. Endocrinology 149:1979–1986

    Article  PubMed  CAS  Google Scholar 

  14. Pielecka-Fortuna J, Moenter SM (2010) Kisspeptin increases gamma-aminobutyric acidergic and glutamatergic transmission directly to gonadotropin-releasing hormone neurons in an estradiol-dependent manner. Endocrinology 151:291–300

    Article  PubMed  CAS  Google Scholar 

  15. Zhang C, Roepke TA, Kelly MJ, Ronnekleiv OK (2008) Kisspeptin depolarizes gonadotropin-­releasing hormone neurons through activation of TRPC-like cationic channels. J Neurosci 28:4423–4434

    Article  PubMed  CAS  Google Scholar 

  16. de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL et al (2003) Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A 100:10972–10976

    Article  PubMed  Google Scholar 

  17. Funes S, Hedrick JA, Vassileva G, Markowitz L, Abbondanzo S et al (2003) The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system. Biochem Biophys Res Commun 312:1357–1363

    Article  PubMed  CAS  Google Scholar 

  18. Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS Jr et al (2003) The GPR54 gene as a regulator of puberty. N Engl J Med 349:1614–1627

    Article  PubMed  CAS  Google Scholar 

  19. Herbison AE, 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 151:312–321

    Article  PubMed  CAS  Google Scholar 

  20. Irwig MS, Fraley GS, Smith JT, Acohido BV, Popa SM et al (2004) Kisspeptin activation of gonadotropin releasing hormone neurons and regulation of KiSS-1 mRNA in the male rat. Neuroendocrinology 80:264–272

    Article  PubMed  CAS  Google Scholar 

  21. Oakley AE, Clifton DK, Steiner RA (2009) Kisspeptin signaling in the brain. Endocr Rev 30:713–743

    Article  PubMed  CAS  Google Scholar 

  22. Zmora N, Stubblefield J, Zulperi Z, Biran J, Levavi-Sivan B et al (2012) Differential and gonad stage-dependent roles of kisspeptin1 and kisspeptin2 in reproduction in the modern teleosts, Morone species. Biol Reprod 86(6):177

    Article  PubMed  Google Scholar 

  23. 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 145:3613–3618

    Article  PubMed  CAS  Google Scholar 

  24. Grone BP, Maruska KP, Korzan WJ, Fernald RD (2010) Social status regulates kisspeptin receptor mRNA in the brain of Astatotilapia burtoni. Gen Comp Endocrinol 169:98–107

    Article  PubMed  CAS  Google Scholar 

  25. Gottsch ML, Cunningham MJ, Smith JT, Popa SM, Acohido BV et al (2004) A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology 145:4073–4077

    Article  PubMed  CAS  Google Scholar 

  26. Matsui H, Takatsu Y, Kumano S, Matsumoto H, Ohtaki T (2004) Peripheral administration of metastin induces marked gonadotropin release and ovulation in the rat. Biochem Biophys Res Commun 320:383–388

    Article  PubMed  CAS  Google Scholar 

  27. Navarro VM, Castellano JM, Fernandez-Fernandez R, Barreiro ML, Roa J et al (2004) Developmental and hormonally regulated messenger ribonucleic acid expression of KiSS-1 and its putative receptor, GPR54, in rat hypothalamus and potent luteinizing hormone-­releasing activity of KiSS-1 peptide. Endocrinology 145:4565–4574

    Article  PubMed  CAS  Google Scholar 

  28. Navarro VM, Castellano JM, Fernandez-Fernandez R, Tovar S, Roa J et al (2005) Effects of KiSS-1 peptide, the natural ligand of GPR54, on follicle-stimulating hormone secretion in the rat. Endocrinology 146:1689–1697

    Article  PubMed  CAS  Google Scholar 

  29. Navarro VM, Castellano JM, Fernandez-Fernandez R, Tovar S, Roa J et al (2005) Characterization of the potent luteinizing hormone-releasing activity of KiSS-1 peptide, the natural ligand of GPR54. Endocrinology 146:156–163

    Article  PubMed  CAS  Google Scholar 

  30. Messager S, Chatzidaki EE, Ma D, Hendrick AG, Zahn D et al (2005) Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc Natl Acad Sci U S A 102:1761–1766

    Article  PubMed  CAS  Google Scholar 

  31. Shahab M, Mastronardi C, Seminara SB, Crowley WF, Ojeda SR et al (2005) Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates. Proc Natl Acad Sci U S A 102:2129–2134

    Article  PubMed  CAS  Google Scholar 

  32. Seminara SB, Dipietro MJ, Ramaswamy S, Crowley WF Jr, Plant TM (2006) Continuous human metastin 45-54 infusion desensitizes G protein-coupled receptor 54-induced gonadotropin-­releasing hormone release monitored indirectly in the juvenile male Rhesus monkey (Macaca mulatta): a finding with therapeutic implications. Endocrinology 147:2122–2126

    Article  PubMed  CAS  Google Scholar 

  33. Plant TM, Ramaswamy S, Dipietro MJ (2006) Repetitive activation of hypothalamic G protein-­coupled receptor 54 with intravenous pulses of kisspeptin in the juvenile monkey (Macaca mulatta) elicits a sustained train of gonadotropin-releasing hormone discharges. Endocrinology 147:1007–1013

    Article  PubMed  CAS  Google Scholar 

  34. Dhillo WS, Chaudhri OB, Patterson M, Thompson EL, Murphy KG et al (2005) Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. J Clin Endocrinol Metab 90:6609–6615

    Article  PubMed  CAS  Google Scholar 

  35. Kitahashi T, Ogawa S, Parhar IS (2009) Cloning and expression of kiss2 in the zebrafish and medaka. Endocrinology 150:821–831

    Article  PubMed  CAS  Google Scholar 

  36. Kanda S, Akazome Y, Matsunaga T, Yamamoto N, Yamada S et al (2008) Identification of KiSS-1 product kisspeptin and steroid-sensitive sexually dimorphic kisspeptin neurons in medaka (Oryzias latipes). Endocrinology 149:2467–2476

    Article  PubMed  CAS  Google Scholar 

  37. Kanda S, Karigo T, Oka Y (2012) Steroid sensitive kiss2 neurones in the goldfish: evolutionary insights into the duplicate kisspeptin gene-expressing neurones. J Neuroendocrinol 24:897–906

    Article  PubMed  CAS  Google Scholar 

  38. Kanda S, Oka Y (2012) Evolutionary insights into the steroid sensitive kiss1 and kiss2 neurons in the vertebrate brain. Front Endocrinol 3:28

    Article  Google Scholar 

  39. 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 151:1751–1759

    Article  PubMed  CAS  Google Scholar 

  40. Smith JT, Cunningham MJ, Rissman EF, Clifton DK, Steiner RA (2005) Regulation of Kiss1 gene expression in the brain of the female mouse. Endocrinology 146:3686–3692

    Article  PubMed  CAS  Google Scholar 

  41. Smith JT, Dungan HM, Stoll EA, Gottsch ML, Braun RE et al (2005) Differential regulation of KiSS-1 mRNA expression by sex steroids in the brain of the male mouse. Endocrinology 146:2976–2984

    Article  PubMed  CAS  Google Scholar 

  42. Revel FG, Saboureau M, Masson-Pevet M, Pevet P, Mikkelsen JD et al (2006) Kisspeptin mediates the photoperiodic control of reproduction in hamsters. Curr Biol 16:1730–1735

    Article  PubMed  CAS  Google Scholar 

  43. Smith JT, Clay CM, Caraty A, Clarke IJ (2007) KiSS-1 messenger ribonucleic acid expression in the hypothalamus of the ewe is regulated by sex steroids and season. Endocrinology 148:1150–1157

    Article  PubMed  CAS  Google Scholar 

  44. Smith JT, Coolen LM, Kriegsfeld LJ, Sari IP, Jaafarzadehshirazi MR et al (2008) Variation in kisspeptin and RFamide-related peptide (RFRP) expression and terminal connections to gonadotropin-releasing hormone neurons in the brain: a novel medium for seasonal breeding in the sheep. Endocrinology 149:5770–5782

    Article  PubMed  CAS  Google Scholar 

  45. Herbison AE, Pape JR (2001) New evidence for estrogen receptors in gonadotropin-releasing hormone neurons. Front Neuroendocrinol 22:292–308

    Article  PubMed  CAS  Google Scholar 

  46. Dorling AA, Todman MG, Korach KS, Herbison AE (2003) Critical role for estrogen receptor alpha in negative feedback regulation of gonadotropin-releasing hormone mRNA expression in the female mouse. Neuroendocrinology 78:204–209

    Article  PubMed  CAS  Google Scholar 

  47. Couse JF, Yates MM, Walker VR, Korach KS (2003) Characterization of the hypothalamic-­pituitary-gonadal axis in estrogen receptor (ER) null mice reveals hypergonadism and endocrine sex reversal in females lacking ERalpha but not ERbeta. Mol Endocrinol 17:1039–1053

    Article  PubMed  CAS  Google Scholar 

  48. Wintermantel TM, Campbell RE, Porteous R, Bock D, Grone HJ et al (2006) Definition of estrogen receptor pathway critical for estrogen positive feedback to gonadotropin-releasing hormone neurons and fertility. Neuron 52:271–280

    Article  PubMed  CAS  Google Scholar 

  49. Adachi S, Yamada S, Takatsu Y, Matsui H, Kinoshita M et al (2007) Involvement of anteroventral periventricular metastin/kisspeptin neurons in estrogen positive feedback action on luteinizing hormone release in female rats. J Reprod Dev 53:367–378

    Article  PubMed  CAS  Google Scholar 

  50. Ansel L, Bolborea M, Bentsen AH, Klosen P, Mikkelsen JD et al (2010) Differential regulation of kiss1 expression by melatonin and gonadal hormones in male and female Syrian hamsters. J Biol Rhythms 25:81–91

    Article  PubMed  CAS  Google Scholar 

  51. Tena-Sempere M (2005) Hypothalamic KiSS-1: the missing link in gonadotropin feedback control? Endocrinology 146:3683–3685

    Article  PubMed  CAS  Google Scholar 

  52. Li D, Mitchell D, Luo J, Yi Z, Cho SG et al (2007) Estrogen regulates KiSS1 gene expression through estrogen receptor alpha and SP protein complexes. Endocrinology 148:4821–4828

    Article  PubMed  CAS  Google Scholar 

  53. Clarkson J, d’Anglemont de Tassigny X, Colledge WH, Caraty A, Herbison AE (2009) Distribution of kisspeptin neurones in the adult female mouse brain. J Neuroendocrinol 21:673–682

    Article  PubMed  CAS  Google Scholar 

  54. Desroziers E, Mikkelsen J, Simonneaux V, Keller M, Tillet Y et al (2010) Mapping of kisspeptin fibres in the brain of the pro-oestrous rat. J Neuroendocrinol 22:1101–1112

    Article  PubMed  CAS  Google Scholar 

  55. Clarkson J, Herbison AE (2006) Postnatal development of kisspeptin neurons in mouse hypothalamus; sexual dimorphism and projections to gonadotropin-releasing hormone neurons. Endocrinology 147:5817–5825

    Article  PubMed  CAS  Google Scholar 

  56. 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 149:4387–4395

    Article  PubMed  CAS  Google Scholar 

  57. Uenoyama Y, Inoue N, Pheng V, Homma T, Takase K et al (2011) Ultrastructural evidence of kisspeptin-gonadotrophin-releasing hormone (GnRH) interaction in the median eminence of female rats: implication of axo-axonal regulation of GnRH release. J Neuroendocrinol 23:863–870

    Article  PubMed  CAS  Google Scholar 

  58. Servili A, Le Page Y, Leprince J, Caraty A, Escobar S et al (2011) Organization of two independent kisspeptin systems derived from evolutionary-ancient kiss genes in the brain of zebrafish. Endocrinology 152:1527–1540

    Article  PubMed  CAS  Google Scholar 

  59. Kanda S, Akazome Y, Okubo K, Okamura H, Oka Y (2009) Kisspeptin neurons act closely but indirectly on GnRH 1 neurons via local interneurons but not on GnRH 2 or 3 neurons in medaka. Society for Neuroscience Abstract. 2009. Chicago, IL

    Google Scholar 

  60. Zhao Y, Wayne NL (2012) Effects of kisspeptin1 on electrical activity of an extrahypothalamic population of gonadotropin-releasing hormone neurons in medaka (Oryzias latipes). PLoS One 7:e37909

    Article  PubMed  CAS  Google Scholar 

  61. 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 169:48–57

    Article  PubMed  CAS  Google Scholar 

  62. Mechaly AS, Vinas J, Piferrer F (2009) Identification of two isoforms of the Kisspeptin-1 receptor (kiss1r) generated by alternative splicing in a modern teleost, the Senegalese sole (Solea senegalensis). Biol Reprod 80:60–69

    Article  PubMed  CAS  Google Scholar 

  63. Biran J, Ben-Dor S, Levavi-Sivan B (2008) Molecular identification and functional characterization of the kisspeptin/kisspeptin receptor system in lower vertebrates. Biol Reprod 79:776–786

    Article  PubMed  CAS  Google Scholar 

  64. Price DA, Greenberg MJ (1977) Structure of a molluscan cardioexcitatory neuropeptide. Science 197:670–671

    Article  PubMed  CAS  Google Scholar 

  65. Lopez-Vera E, Aguilar MB, Heimer de la Cotera EP (2008) FMRFamide and related peptides in the phylum mollusca. Peptides 29:310–317

    Article  PubMed  CAS  Google Scholar 

  66. Osugi T, Daukss D, Gazda K, Ubuka T, Kosugi T et al (2012) Evolutionary origin of the structure and function of gonadotropin-inhibitory hormone: insights from lampreys. Endocrinology 153(5):2362–2374

    Article  PubMed  CAS  Google Scholar 

  67. Osugi T, Ukena K, Sower SA, Kawauchi H, Tsutsui K (2006) Evolutionary origin and divergence of PQRFamide peptides and LPXRFamide peptides in the RFamide peptide family. Insights from novel lamprey RFamide peptides. FEBS J 273:1731–1743

    Article  PubMed  CAS  Google Scholar 

  68. Osugi T, Uchida K, Nozaki M, Tsutsui K (2011) Characterization of novel RFamide peptides in the central nervous system of the brown hagfish: isolation, localization, and functional analysis. Endocrinology 152:4252–4264

    Article  PubMed  CAS  Google Scholar 

  69. Larhammar D, Lundin LG, Hallbook F (2002) The human Hox-bearing chromosome regions did arise by block or chromosome (or even genome) duplications. Genome Res 12:1910–1920

    Article  PubMed  CAS  Google Scholar 

  70. Lyubimov Y, Engstrom M, Wurster S, Savola JM, Korpi ER et al (2010) Human kisspeptins activate neuropeptide FF2 receptor. Neuroscience 170:117–122

    Article  PubMed  CAS  Google Scholar 

  71. Oishi S, Misu R, Tomita K, Setsuda S, Masuda R et al (2011) Activation of neuropeptide FF receptors by kisspeptin receptor ligands. ACS Med Chem Lett 2:53–57

    Article  CAS  Google Scholar 

  72. Gouarderes C, Mazarguil H, Mollereau C, Chartrel N, Leprince J et al (2007) Functional differences between NPFF1 and NPFF2 receptor coupling: high intrinsic activities of RFamide-­related peptides on stimulation of [35S]GTPgammaS binding. Neuropharmacology 52:376–386

    Article  PubMed  CAS  Google Scholar 

  73. Clarke IJ, Qi Y, Puspita Sari I, Smith JT (2009) Evidence that RF-amide related peptides are inhibitors of reproduction in mammals. Front Neuroendocrinol 30(3):371–378

    Article  PubMed  CAS  Google Scholar 

  74. Clarke IJ, Sari IP, Qi Y, Smith JT, Parkington HC et al (2008) Potent action of RFamide-related peptide-3 on pituitary gonadotropes indicative of a hypophysiotropic role in the negative regulation of gonadotropin secretion. Endocrinology 149:5811–5821

    Article  PubMed  CAS  Google Scholar 

  75. Gibson EM, Humber SA, Jain S, Williams WP III, Zhao S et al (2008) Alterations in RFamide-­related peptide expression are coordinated with the preovulatory luteinizing hormone surge. Endocrinology 149:4958–4969

    Article  PubMed  CAS  Google Scholar 

  76. Anderson GM, Relf HL, Rizwan MZ, Evans JJ (2009) Central and peripheral effects of RFamide-related peptide-3 on luteinizing hormone and prolactin secretion in rats. Endocrinology 150:1834–1840

    Article  PubMed  CAS  Google Scholar 

  77. Kadokawa H, Shibata M, Tanaka Y, Kojima T, Matsumoto K et al (2009) Bovine C-terminal octapeptide of RFamide-related peptide-3 suppresses luteinizing hormone (LH) secretion from the pituitary as well as pulsatile LH secretion in bovines. Domest Anim Endocrinol 36:219–224

    Article  PubMed  CAS  Google Scholar 

  78. Kriegsfeld LJ, Mei DF, Bentley GE, Ubuka T, Mason AO et al (2006) Identification and ­characterization of a gonadotropin-inhibitory system in the brains of mammals. Proc Natl Acad Sci U S A 103:2410–2415

    Article  PubMed  CAS  Google Scholar 

  79. Tsutsui K, Ubuka T, Bentley GE, Kriegsfeld LJ (2012) Gonadotropin-inhibitory hormone (GnIH): discovery, progress and prospect. Gen Comp Endocrinol 177(3):305–314

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yoshitaka Oka Ph.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Kanda, S., Oka, Y. (2013). Structure, Synthesis, and Phylogeny of Kisspeptin and its Receptor. In: Kauffman, A., Smith, J. (eds) Kisspeptin Signaling in Reproductive Biology. Advances in Experimental Medicine and Biology, vol 784. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6199-9_2

Download citation

Publish with us

Policies and ethics