Kiss1r, the receptor for kisspeptin, is a G protein-coupled receptor that activates the G proteins Gαq/11. Kisspeptin/Kiss1r signaling is a key regulator of the neuroendocrine-reproductive axis, playing essential roles in the onset of puberty and control of the hypothalamic-pituitary-gonadal axis [2,3,5,6,9]. It also has implications in other biological processes such as airway remodeling and tumor metastasis [1,4].

In mouse models, inactivating mutations in Kiss1r cause idiopathic hypogonadotropic hypogonadism, revealing its role in regulating testosterone production. Knockdown of Kiss1r in MA-10 mouse Leydig tumor cells reduced progesterone production, associated with decreased luteinizing hormone/choriogonadotropin receptor and StAR protein expressions [7]. Lesions of Kiss1r-containing cells in the arcuate nucleus of female sheep disrupted the amplitude and regularity of LH pulses, suggesting Kiss1r-positive neurons form part of a positive feedback circuit reinforcing the activity of the KNDy neural network [8].

In conclusion, Kiss1r is crucial for the normal functioning of the reproductive system, regulating processes like puberty onset, gonadal function, and pregnancy. Model-based research, especially using gene-knockout models in mice and lesion studies in sheep, has provided valuable insights into its role in reproductive diseases such as idiopathic hypogonadotropic hypogonadism.