Understanding the functions of kisspeptin and kisspeptin receptor (Kiss1R) from clinical case studies.

It is widely acknowledged that kisspeptin and its receptor Kiss1R play central regulatory roles in the hypothalamus-pituitary-gonad (HPG) axis and reproduction. Mutations of KISS1 and KISS1R lead to disorders associated with pubertal development, such as central precocious puberty (CPP) and idiopathic hypogonadotropic hypogonadism (IHH). This review focuses on KISS1 and KISS1R mutations found in CPP and IHH and its purposes are twofold: Firstly, based on the mutations found in KISS1 and KISS1R, this review provides insights into the precise mechanism of kisspeptin and the kisspeptin/Kiss1R pathway in the reproductive axis and in puberty. Secondly, G protein-coupled receptors (GPCRs) are known to share highly conserved structural motifs; therefore, knowledge of mutations found at different structural domains of Kiss1R in the diseased state, and how they affect Kiss1R function can be used to decipher GPCR domain function.