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Kisspeptin expression in the brain: catalyst for the initiation of puberty

J T Smith1, I J Clarke

  • 1Department Physiology, Monash University, P. O. Box 13F, Clayton, Melbourne, VIC, 3800, Australia.

Reviews in Endocrine & Metabolic Disorders
|March 6, 2007
PubMed

Insights

Mutations in G protein coupled receptor 54 (GPR54) cause hypogonadotropic hypogonadism. Kisspeptins, GPR54 ligands, are crucial regulators of gonadotropin-releasing hormone (GnRH) and puberty initiation.

Area of Science:

  • Neuroendocrinology
  • Reproductive biology
  • Genetics

Background:

  • G protein coupled receptor 54 (GPR54) mutations were discovered to cause hypogonadotropic hypogonadism in mice and humans.
  • Kisspeptins, the natural ligands for GPR54, are key regulators of reproductive neuroendocrine function.

Purpose of the Study:

  • To elucidate the role of kisspeptins and GPR54 in regulating gonadotropin-releasing hormone (GnRH) secretion.
  • To understand the function of kisspeptin in mediating steroid feedback to the GnRH system.
  • To investigate the involvement of kisspeptin in the initiation of puberty.

Main Methods:

  • Inactivation of GPR54 gene in mice and analysis of human patients with mutations.
  • Administration of kisspeptins centrally or peripherally to assess effects on gonadotropin secretion.
  • Localization of KiSS-1 gene expression in the hypothalamus.
  • Analysis of KiSS-1 expression regulation by gonadal steroids and the estrous cycle.

Main Results:

  • Inactivating mutations in GPR54 lead to hypogonadotropic hypogonadism.
  • Kisspeptins potently stimulate gonadotropin secretion.
  • KiSS-1 expression is found in specific hypothalamic regions and is modulated by steroids and the estrous cycle.
  • Kisspeptin signaling appears essential for initiating puberty and mediating estrogen-induced positive feedback on GnRH release.

Conclusions:

  • Kisspeptins are critical regulators of GnRH secretion and reproductive function.
  • Kisspeptin acts as a key intermediary for steroid feedback to GnRH neurons.
  • Kisspeptin signaling is fundamental for pubertal development.

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