Kisspeptin Neurons as Drivers of Reproductive Development

Abstract

A network of hypothalamic neurons integrates signals from the environment, the brain and the endocrine system to initiate puberty and sustain fertility. In the last decade, kisspeptin neurons have emerged as essential players in this network. In this dissertation, I review some of the landmark studies that shaped our understanding of how the brain regulates reproduction. I then describe three lines of investigation from my research. First, I characterize transgenic mice that were developed to understand the function of kisspeptin neurons. Second, I set out to resolve a controversy about the requirement of kisspeptin neurons for puberty and the ability of compensatory pathways to overcome their ablation. I discovered that the gene that encodes kisspeptin (Kiss1) is expressed in excess of levels required for fertility in mice, reflecting a failsafe to guarantee reproductive success. I also found that females require larger quantities of kisspeptin to reproduce than males, due to their need of kisspeptin for ovulation. Finally, I provide evidence that kisspeptin neurons implicated in ovulation are scarcer in males than females as a result of lower Kiss1 expression rather than due to sex differences in the death or birth of kisspeptin neurons. I conclude with implications of this work and explore possible future directions for understanding the development of kisspeptin neurons.