Skip to main content

Developmental Changes in the Expression of Kisspeptin mRNA in Rat Hypothalamus

Journal of Molecular Neuroscience volume 43, pages 138–145 (2011)Cite this article

Abstract

Kisspeptin is a family of neuropeptides and the natural ligands of G protein-coupled receptor (GPR)-54. Kisspeptin/GPR-54 system is known to play a pivotal role in puberty onset and in the regulation of reproductive functions. To clarify the postnatal ontogeny of kisspeptin neurons in rat hypothalamus, we analyzed the expression patterns of kisspeptin mRNA from neonate to adult by in situ hybridization. In anteroventral periventricular nucleus (AVPV), kisspeptin mRNA were first detected at postnatal day (PND) 7 and postnatal week 3 in males and females, respectively, and the number of kisspeptin mRNA-expressing neurons increased during development in both sexes. In the arcuate nucleus (ARC), kisspeptin mRNA was present from PND3. In males, the number of kisspeptin mRNA-expressing neurons gradually increased during development. In females, the number of kisspeptin mRNA-expressing neurons in neonates was greater than in males; it significantly decreased at juvenile stages and then increased toward adulthood. These results indicate that the increase in kisspeptin mRNA expression in ARC across puberty might be involved in the onset of puberty. We also demonstrate that the kisspeptin mRNA-expressing neurons in ARC appear earlier than those in AVPV and show clear sex differences in their numbers during neonatal period.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Figure 1
Figure 2
Figure 3

References

  • Adachi S, Yamada S, Takatsu Y 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

    CAS  Article  PubMed  Google Scholar 

  • Bentsen AH, Ansel L, Simonneaux V, Tena-Sempere M, Juul A, Mikkelsen JD (2010) Maturation of kisspeptinergic neurons coincides with puberty onset in male rats. Peptides 31:275–283

    CAS  Article  PubMed  Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

  • Clarkson J, d'Anglemont de Tassigny X, Moreno AS, Colledge WH, Herbison AE (2008) Kisspeptin-GPR54 signaling is essential for preovulatory gonadotropin-releasing hormone neuron activation and the luteinizing hormone surge. J Neurosci 28:8691–8697

    CAS  Article  PubMed  Google Scholar 

  • Clarkson J, Boon WC, Simpson ER, Herbison AE (2009) Postnatal development of an estradiol-kisspeptin positive feedback mechanism implicated in puberty onset. Endocrinology 150:3214–3220

    CAS  Article  PubMed  Google Scholar 

  • d'Anglemont de Tassigny X, Fagg LA, Dixon JP et al (2007) Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene. Proc Natl Acad Sci USA 104:10714–10719

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Decourt C, Tillet Y, Caraty A, Franceschini I, Briant C (2008) Kisspeptin immunoreactive neurons in the equine hypothalamus Interactions with GnRH neuronal system. J Chem Neuroanat 36:131–137

    CAS  Article  PubMed  Google Scholar 

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

    CAS  Article  PubMed  Google Scholar 

  • Dohler KD, Wuttke W (1975) Changes with age in levels of serum gonadotropins, prolactin and gonadal steroids in prepubertal male and female rats. Endocrinology 97:898–907

    CAS  Article  PubMed  Google Scholar 

  • Funes S, Hedrick JA, Vassileva G 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

    CAS  Article  PubMed  Google Scholar 

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

    CAS  Article  PubMed  Google Scholar 

  • Han SK, Gottsch ML, Lee KJ 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

    CAS  Article  PubMed  Google Scholar 

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

    CAS  Article  PubMed  Google Scholar 

  • Kauffman AS, Gottsch ML, Roa J et al (2007) Sexual differentiation of Kiss1 gene expression in the brain of the rat. Endocrinology 148:1774–1783

    CAS  Article  PubMed  Google Scholar 

  • Kotani M, Detheux M, Vandenbogaerde A 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

    CAS  Article  PubMed  Google Scholar 

  • Lapatto R, Pallais JC, Zhang D et al (2007) Kiss1-/- mice exhibit more variable hypogonadism than Gpr54-/- mice. Endocrinology 148:4927–4936

    CAS  Article  PubMed  Google Scholar 

  • Lee DK, Nguyen T, O'Neill GP et al (1999) Discovery of a receptor related to the galanin receptors. FEBS Lett 446:103–107

    CAS  Article  PubMed  Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

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

    CAS  Article  PubMed  Google Scholar 

  • Muir AI, Chamberlain L, Elshourbagy NA et al (2001) AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1. J Biol Chem 276:28969–28975

    CAS  Article  PubMed  Google Scholar 

  • Navarro VM, Castellano JM, Fernandez-Fernandez R et al (2004a) 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

    CAS  Article  PubMed  Google Scholar 

  • Navarro VM, Fernandez-Fernandez R, Castellano JM et al (2004b) Advanced vaginal opening and precocious activation of the reproductive axis by KiSS-1 peptide, the endogenous ligand of GPR54. J Physiol 561:379–386

    CAS  Article  PubMed  Google Scholar 

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

    CAS  Article  PubMed  Google 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 149:4387–4395

    CAS  Article  PubMed  Google Scholar 

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

    CAS  Article  PubMed  Google Scholar 

  • Shahab M, Mastronardi C, Seminara SB, Crowley WF, Ojeda SR, Plant TM (2005) Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates. Proc Natl Acad Sci USA 102:2129–2134

    CAS  Article  PubMed  Google Scholar 

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

    CAS  Article  PubMed  Google Scholar 

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

    CAS  Article  PubMed  Google Scholar 

  • Smith JT, Popa SM, Clifton DK, Hoffman GE, Steiner RA (2006) Kiss1 neurons in the forebrain as central processors for generating the preovulatory luteinizing hormone surge. J Neurosci 26:6687–6694

    CAS  Article  PubMed  Google Scholar 

  • Takase K, Uenoyama Y, Inoue N et al (2009) Possible role of oestrogen in pubertal increase of Kiss1/kisspeptin expression in discrete hypothalamic areas of female rats. J Neuroendocrinol 21:527–537

    CAS  Article  PubMed  Google Scholar 

  • Terao Y, Kumano S, Takatsu Y et al (2004) Expression of KiSS-1, a metastasis suppressor gene, in trophoblast giant cells of the rat placenta. Biochim Biophys Acta 1678:102–110

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to Takeda Pharmaceutical Company for kindly providing rat KiSS-1 cDNA. This work was supported by the Grant-in-Aids from Ministry of Education, Science, Sports and Culture, Japan (#S0801035, 22590230 to H.O.), and Naito Foundation (to H.O.).

Author information

Affiliations

  1. Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan

    Ken Takumi, Norio Iijima & Hitoshi Ozawa

Authors
  1. Ken Takumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Norio Iijima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hitoshi Ozawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hitoshi Ozawa.

Additional information

This study was presented at GPCR2010 Symposium, the official satellite symposium of the 14th International Congress of Endocrinology, Kyoto

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Takumi, K., Iijima, N. & Ozawa, H. Developmental Changes in the Expression of Kisspeptin mRNA in Rat Hypothalamus. J Mol Neurosci 43, 138–145 (2011). https://doi.org/10.1007/s12031-010-9430-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-010-9430-1

Keywords

  • Kisspeptin
  • G protein-coupled receptor-54
  • Reproduction
  • Development
  • Sex difference