Abstract
The hypothalamic hormone GnRH has traditionally been viewed as a central driver of the hypothalamic-pituitary-gonadal axis. Pulsatile GnRH release is required for pulsatile gonadotropin secretion, which then modulates gonadal steroid feedback and brings about full fertility in the adult. Pathways governing GnRH ontogeny and physiology have been discovered by studying humans with disorders of GnRH secretion. In this chapter, the human genetics of the kisspeptin signaling pathway in patients with diverse reproductive phenotypes will be explored. The discovery of defects in the kisspeptin system in several reproductive disorders has shed light on the mechanisms involved in regulating GnRH secretion, revealing the critical role played by the kisspeptin signaling pathway in pubertal initiation and reproductive function.
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Acknowledgments
Dr. Seminara and some of the data referenced in this article were supported by the Eunice Kennedy Shriver NICHD/NIH through cooperative agreement [U54 HD028138] as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research, as well as R01 HD043341 and K24 HD067388.
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Silveira, L.G., Latronico, A.C., Seminara, S.B. (2013). Kisspeptin and Clinical Disorders. In: Kauffman, A., Smith, J. (eds) Kisspeptin Signaling in Reproductive Biology. Advances in Experimental Medicine and Biology, vol 784. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6199-9_9
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