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. 2009 Nov 27;312(1-2):61-71. doi: 10.1016/j.mce.2008.11.017. Epub 2008 Nov 25.


Kisspeptins, the products of KiSS-1 gene, have recently emerged as fundamental regulators of reproductive function in different mammalian and, presumably, non-mammalian species. To date, a single form of KiSS-1 has been described in mammals, and recently, in several fish species and Xenopus. We report herein the cloning and characterization of two distinct KiSS-like genes, namely, KiSS-1 and KiSS-2, in the teleost sea bass. While KiSS-1 encodes a peptide identical to rodent kisspeptin-10, the predicted KiSS-2 decapeptide diverges at 4 amino acids (FNFNPFGLRF). Genome database searches showed that both genes are present in non-placental vertebrate genomes. Indeed, phylogenetic and genome mapping analyses suggest that KiSS-1 and KiSS-2 are paralogous genes that originated by duplication of an ancestral gene, although KiSS-2 is lost in placental mammals. KiSS-1 and KiSS-2 mRNAs are present in brain and gonads of sea bass, medaka and zebrafish. Comparative functional studies demonstrated that KiSS-2 decapeptide was significantly more potent than KiSS-1 peptide in inducing LH and FSH secretion in sea bass. In contrast, KiSS-2 decapeptide only weakly elicited LH secretion in rats, whereas KiSS-1 peptide was maximally effective. Our data are the first to provide conclusive evidence for the existence of a second KiSS gene, KiSS-2, in non-placental vertebrates, whose product is likely to play a dominant stimulatory role in the regulation of the gonadotropic axis at least in teleosts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Amino Acid Sequence
  • Analysis of Variance
  • Animals
  • Base Sequence
  • Bass / genetics
  • Bass / metabolism
  • Cloning, Molecular
  • Female
  • Fish Proteins / chemistry
  • Fish Proteins / genetics*
  • Fish Proteins / metabolism
  • Gonadotropins, Pituitary / blood
  • Kisspeptins
  • Male
  • Molecular Sequence Data
  • Organ Specificity
  • Oryzias / genetics
  • Oryzias / metabolism
  • Phylogeny
  • Proteins / chemistry
  • Proteins / genetics*
  • Proteins / metabolism
  • Rats
  • Rats, Wistar
  • Reproduction / genetics*
  • Seasons
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Synteny
  • Time Factors
  • Vertebrates / genetics*
  • Vertebrates / metabolism
  • Zebrafish / genetics
  • Zebrafish / metabolism
  • Zebrafish Proteins / chemistry
  • Zebrafish Proteins / genetics*
  • Zebrafish Proteins / metabolism


  • Fish Proteins
  • Gonadotropins, Pituitary
  • Kiss1 protein, rat
  • Kiss1 protein, zebrafish
  • Kisspeptins
  • Proteins
  • Zebrafish Proteins

Associated data

  • GENBANK/FJ008914
  • GENBANK/FJ008915