Disease relevance of Kiss1r

• The discovery that, in both humans and mouse models, loss-of-function mutations in the gene that encodes G-protein-coupled receptor 54 result in phenotypes of hypogonadotropic hypogonadism with an absence of pubertal development has unearthed a novel pathway regulating GnRH secretion [1].
• Furthermore, activation of the KiSS1 receptor inhibits cell proliferation and cell migration, key characteristics of tumor metastasis [2].

High impact information on Kiss1r

• Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54 [3].
• The Kiss1 gene encodes a family of neuropeptides called kisspeptins, which activate the receptor G protein-coupled receptor-54 and play a role in the neuroendocrine regulation of GnRH secretion [4].
• Recently, loss of function mutations of the gene encoding G protein-coupled receptor 54 (GPR54), the putative receptor for the KiSS-1-derived peptide metastin, have been associated with lack of puberty onset and hypogonadotropic hypogonadism [5].
• These data suggest a role for GPR54/KiSS-1 in normal sexual development, and indicate that study of the GPR54 mutant mice may provide valuable insights into human reproductive syndromes [6].
• The analysis of the GPR54 mutant mice revealed developmental abnormalities of both male and female genitalia and histopathological changes in tissues which normally contain sexually dimorphic features [6].

Regulatory relationships of Kiss1r

• Diet-induced obesity or obesity associated with leptin deficiency (ob/ob vs. wild-type mice) failed to induce overt changes in hypothalamic expression of KiSS-1 and GPR54 genes [7].

References