Figure 2. Neuroanatomy of kisspeptin-GnRH pathway and the control of HPG axis in humans and rodents. Kisspeptin signals directly to GnRH neurons, which express KISS1R. The location of kisspeptin neurons within the hypothalamus is species specific, residing within the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus in rodents, and within the preoptic area (POA) and the infundibular nucleus in humans. Kisspeptin neurons in the infundibular nucleus (humans)/arcuate nucleus (rodents) co-express neurokinin B and dynorphin (KNDy neurons), which autosynaptically regulate kisspeptin secretion (via neurokinin B receptor and kappa opioid peptide receptor). In humans, infundibular KNDy neurons relay negative (red) and positive (green) feedbacks, whereas in rodents the negative and positive steroid feedbacks are mediated via arcuate nucleus and AVPV respectively. The role of human POA kisspeptin neurons in sex steroid feedback is not yet clear. (Adapted from: Skorupskaite K, George JT, Anderson RA. The kisspeptin-GnRH pathway in human reproductive health and disease. Human Reproduction Update. 2014;20:485-500)