Driving reproduction: RFamide peptides behind the wheel

Horm Behav. 2006 Dec;50(5):655-66. doi: 10.1016/j.yhbeh.2006.06.004. Epub 2006 Jul 31.


The availability of tools for probing the genome and proteome more efficiently has allowed for the rapid discovery of novel genes and peptides that play important, previously uncharacterized roles in neuroendocrine regulation. In this review, the role of a class of neuropeptides containing the C-terminal Arg-Phe-NH(2) (RFamide) in regulating the reproductive axis will be highlighted. Neuropeptides containing the C-terminal Phe-Met-Arg-Phe-NH(2) (FMRFamide) were first identified as cardioregulatory elements in the bi-valve mollusk Macrocallista nimbosa. During the past two decades, numerous studies have shown the presence of structurally similar peptides sharing the RFamide motif across taxa. In vertebrates, RFamide peptides have pronounced influences on opiatergic regulation and neuroendocrine function. Two key peptides in this family are emerging as important regulators of the reproductive axis, kisspeptin and gonadotropin-inhibitory hormone (GnIH). Kisspeptin acts as the accelerator, directly driving gonadotropin-releasing hormone (GnRH) neurons, whereas GnIH acts as the restraint. Recent evidence suggests that both peptides play a role in mediating the negative feedback effects of sex steroids. This review presents the hypothesis that these peptides share complementary roles by responding to internal and external stimuli with opposing actions to precisely regulate the reproductive axis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Avian Proteins / physiology
  • Birds
  • Brain Chemistry
  • Female
  • Glycoproteins / physiology
  • Humans
  • Hypothalamic Hormones / physiology
  • Kisspeptins
  • Male
  • Mammals
  • Models, Biological
  • Molecular Sequence Data
  • Neuropeptides / physiology*
  • Protein Precursors / chemistry
  • Reproduction / drug effects
  • Reproduction / physiology*
  • Sequence Alignment
  • Sexual Behavior, Animal / drug effects
  • Tumor Suppressor Proteins / physiology


  • Avian Proteins
  • Glycoproteins
  • Hypothalamic Hormones
  • KISS1 protein, human
  • Kisspeptins
  • Neuropeptides
  • Protein Precursors
  • RFamide peptide
  • Tumor Suppressor Proteins
  • gonadotropin inhibitor
  • gonadotropin-inhibitory hormone, Coturnix japonica
  • prepro-gonad-inhibiting hormone
  • arginylphenylalaninamide