The cartilaginous fish are considered to be the phylogenetically oldest jawed vertebrates. In spite of their morphological conservation during 400 million years of evolution, expression of gonadotropin-releasing hormone (GnRH) structural variants in the brain varies profoundly among species. The dominant form of this neuropeptide is [His⁵Trp⁷Tyr⁸]-GnRH (chicken GnRH-II) and may have been the original hypothalamic gonadotropin-releasing factor in jawed vertebrates. Indeed, both this form and the related [His⁵Trp⁷Leu⁸]-GnRH (dogish GnRH), are potent at gonadotropin release in mammalian-based systems. The presence of GnRH-binding substances and high concentrations of chicken GnRH-II in the systemic blood suggest the chondrichthyan system evolved to transport GnRH to the gonadotropes via the systemic circulation.