Roles of copper in neurokinin B and gonadotropin-releasing hormone structure and function and the endocrinology of reproduction

Copper is a metal ion present in all organisms, where it has well-known roles in association with proteins and enzymes essential for cellular processes. In the early decades of the twentieth century copper was shown to influence mammalian reproductive biology, and it was subsequently shown to exert effects primarily at the level of the pituitary gland and/or hypothalamic regions of the brain. Furthermore, it has been reported that copper can interact with key neuropeptides in the hypothalamic-pituitary-gonadal axis, notably gonadotropin-releasing hormone (GnRH) and neurokinin B. Interestingly, recent phylogenetic analysis of the sequences of GnRH-related peptides indicates that copper binding is an evolutionarily ancient property of this neuropeptide family, which has been variously retained, modified or lost in the different taxa. In this mini-review the metal-binding properties of neuropeptides in the vertebrate reproductive pathway are reviewed and the evolutionary and functional significance of copper binding by GnRH-related neuropeptides in vertebrates and invertebrates are discussed.