Kisspeptin receptor (Kiss1r) (Kiss1r)

The Kisspeptin receptor (Kiss1r), also known as GPR54, is a G protein-coupled receptor that plays a fundamental role in the neuroendocrine control of reproduction in rats [1, 4]. It is primarily expressed on gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus, where its activation by endogenous kisspeptin ligands triggers the release of GnRH [3, 6]. This signaling pathway is the primary driver for the onset of puberty and the maintenance of the hypothalamic-pituitary-gonadal (HPG) axis, regulating the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) [9, 13]. Beyond its reproductive functions, Kiss1r was originally identified as a metastasis suppressor and is involved in regulating metabolic processes such as insulin secretion and glucose homeostasis [3, 8]. Dysregulation of the Kiss1r system is linked to clinical conditions such as hypogonadotropic hypogonadism, precocious puberty, and certain hormone-sensitive cancers [4, 11]. Pharmacological agents targeting Kiss1r, including potent agonists like MVT-602 and antagonists like Peptide 234, are being explored for applications in treating infertility, managing sex steroid-dependent diseases, and potentially controlling tumor progression [3, 19]. However, therapeutic use must account for receptor desensitization, which can lead to the suppression of the reproductive axis during chronic administration [18].

Other names

KiSS-1 receptorG-protein coupled receptor 54GPR54Metastin receptorAXOR12rOT7T175KiSS-1RKisspeptins receptor

Agonism of the Kiss1r receptor stimulates the hypothalamic-pituitary-gonadal axis by inducing GnRH release, while antagonism or chronic desensitization inhibits this axis.