Sex Steroid Regulation of Kisspeptin Circuits

Kisspeptin cells appear to be the "missing link," bridging the divide between levels of gonadal steroids and feedback control of gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin neurons are important in the generation of both sex steroid negative and estrogen positive feedback signals to GnRH neurons, the former being involved in the tonic regulation of GnRH secretion in males and females and the latter governing the preovulatory GnRH/luteinizing hormone (LH) surge in females. In rodents, kisspeptin-producing cells populate the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (ARC), and estrogen regulation of kisspeptin has been extensively studied in these regions. Kisspeptin cells in the ARC appear to receive and forward signals applicable to negative feedback regulation of GnRH. In the female rodent AVPV, kisspeptin cells are important for positive feedback regulation of GnRH and the preovulatory LH surge. In sheep and primates, a rostral population of kisspeptin cells is located in the dorsolateral preoptic area (POA) as well as the ARC. Initial studies showed kisspeptin cells in the latter were involved in both the positive and negative feedback regulation of GnRH. Interestingly, further studies now suggest that kisspeptin cells in the ovine POA may also play an important role in generating estrogen positive feedback. This chapter discusses the current consensus knowledge regarding the interaction between sex steroids and kisspeptin neurons in mammals.