Neuronal circuits in the hypothalamus controlling gonadotrophin-releasing hormone release: the neuroanatomical projections of kisspeptin neurons

Exp Physiol. 2013 Nov;98(11):1544-9. doi: 10.1113/expphysiol.2013.071944. Epub 2013 Aug 9.


The hypothalamus regulates the key hormonal signalling events essential for reproduction and fertility in mammals. The gonadotrophin-releasing hormone (GnRH) neurons are the principal neurons of the complex neuronal network that co-ordinates multiple internal homeostatic and external factors necessary for fertility. Kisspeptin neurons are one of the major regulators of GnRH neuronal activity, but the ways in which kisspeptin neurons, located in the arcuate nucleus (ARN) and rostral periventricular area of the third ventricle (RP3V), control GnRH neurons are poorly understood. This study focused on the use of anterograde and retrograde tracing techniques to establish the neuronal projection patterns of kisspeptin cells in the female mouse brain. Both anterograde and retrograde tracing studies highlight the complexity of the kisspeptin neuronal system and indicate that both ARN and RP3V kisspeptin neurons may participate in a variety of limbic functions. In relationship to the GnRH neuronal network, these investigations demonstrate that rostral ARN kisspeptin neurons may also project to GnRH neuronal cell bodies. However, we found no anatomical evidence to suggest that kisspeptin neurons innervate GnRH nerve terminals in the external layer of the median eminence. These studies provide a neuroanatomical framework for the further elucidation of the functions of the ARN and RP3V kisspeptin neuron populations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arcuate Nucleus of Hypothalamus / metabolism*
  • Female
  • Gonadotropin-Releasing Hormone / metabolism*
  • Hypothalamus / physiology*
  • Kisspeptins / physiology
  • Mice
  • Neural Pathways / physiology
  • Neuroanatomical Tract-Tracing Techniques / methods
  • Neurons / physiology*
  • Third Ventricle / metabolism


  • Kisspeptins
  • Gonadotropin-Releasing Hormone