Kisspeptins are neuropeptides synthesized in the hypothalamus and encoded by theKISS1 gene. The KISS1 gene encodes theG protein-coupled receptor 54 (known as KISS1R or GPR54) and plays a crucial role in regulating reproduction, pubertal maturation, and metabolic function.[11][12][13] KISS1 neurons located in thearcuate nucleus (ARC) of themediobasal hypothalamus (MBH) project toGnRH neurons in the median eminence, which expresses KISS1R, to stimulateLH secretions in a pulsatile manner from the anterior pituitary to initiate ovulation/ pubertal maturation.[14][15][16] The KISS1 and KISS1R/GPR54 genes have been detected in the brain, pituitary, placenta, pancreas, liver, and small intestine.[14]
Kisspeptin is involved in the regulation of endocrine function and the onset ofpuberty, with activation of the kisspeptin receptor triggering release ofgonadotropin-releasing hormone (GnRH),[17][18] and release of kisspeptin itself being inhibited byoestradiol but enhanced by GnRH.[19] Reductions in kisspeptin levels with age may conversely be one of the reasons behind age-related declines in levels of other endocrine hormones such asluteinizing hormone.[20]
Alterations in the KISS1/KISS1R signaling pathway have been linked to multiple physiological conditions, including metabolic and reproductive abnormalities.[21] A knockout model of GPR54/KISS1R in mice showed hypogonadism, and the mice failed to reach puberty.[21] The KISS1 gene has been stated to suppress the metastasis of malignant melanomas.[22] KISS1R signaling pathway has been characterized in the suppression of tumors and has anti-metastatic effects in several cancers, including breast cancer.[23][24]
Activation of KISS1R elicits a neuroendocrine response leading to pubertal maturation. This is indicated by intermittent kisspeptin-10 administration to pre-pubertal animals resulting in activation of thehypothalamic-pituitary axis and subsequentprecocious puberty in rats and primates.[25][26] Mutations in the kisspeptin receptor KISS1R have resulted inisolated hypogonadotropic hypogonadism (IHH), characterized by delayed or absence of puberty[27]
^Navarro VM, Castellano JM, Fernández-Fernández R, Barreiro ML, Roa J, Sanchez-Criado JE, et al. (October 2004). "Developmental and hormonally regulated messenger ribonucleic acid expression of KiSS-1 and its putative receptor, GPR54, in rat hypothalamus and potent luteinizing hormone-releasing activity of KiSS-1 peptide".Endocrinology.145 (10):4565–4574.doi:10.1210/en.2004-0413.PMID15242985.S2CID14817781.
^Plant TM, Ramaswamy S, Dipietro MJ (February 2006). "Repetitive activation of hypothalamic G protein-coupled receptor 54 with intravenous pulses of kisspeptin in the juvenile monkey (Macaca mulatta) elicits a sustained train of gonadotropin-releasing hormone discharges".Endocrinology.147 (2):1007–1013.doi:10.1210/en.2005-1261.PMID16282350.
^Richard N, Galmiche G, Corvaisier S, Caraty A, Kottler ML (March 2008). "KiSS-1 and GPR54 genes are co-expressed in rat gonadotrophs and differentially regulated in vivo by oestradiol and gonadotrophin-releasing hormone".Journal of Neuroendocrinology.20 (3):381–393.doi:10.1111/j.1365-2826.2008.01653.x.PMID18208554.S2CID205345039.
^abFunes S, Hedrick JA, Vassileva G, Markowitz L, Abbondanzo S, Golovko A, et al. (December 2003). "The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system".Biochemical and Biophysical Research Communications.312 (4):1357–1363.doi:10.1016/j.bbrc.2003.11.066.PMID14652023.
^Guzman S, Brackstone M, Wondisford F, Babwah AV, Bhattacharya M (July 2019). "KISS1/KISS1R and Breast Cancer: Metastasis Promoter".Seminars in Reproductive Medicine.37 (4):197–206.doi:10.1055/s-0039-3400968.PMID31972865.S2CID210883188.
^Plant TM, Ramaswamy S, Dipietro MJ (February 2006). "Repetitive activation of hypothalamic G protein-coupled receptor 54 with intravenous pulses of kisspeptin in the juvenile monkey (Macaca mulatta) elicits a sustained train of gonadotropin-releasing hormone discharges".Endocrinology.147 (2):1007–1013.doi:10.1210/en.2005-1261.PMID16282350.
Seminara SB (2006). "Metastin and its G protein-coupled receptor, GPR54: critical pathway modulating GnRH secretion".Frontiers in Neuroendocrinology.26 (3–4):131–138.doi:10.1016/j.yfrne.2005.10.001.PMID16309735.S2CID40864875.
Clements MK, McDonald TP, Wang R, Xie G, O'Dowd BF, George SR, et al. (June 2001). "FMRFamide-related neuropeptides are agonists of the orphan G-protein-coupled receptor GPR54".Biochemical and Biophysical Research Communications.284 (5):1189–1193.doi:10.1006/bbrc.2001.5098.PMID11414709.
Hori A, Honda S, Asada M, Ohtaki T, Oda K, Watanabe T, et al. (September 2001). "Metastin suppresses the motility and growth of CHO cells transfected with its receptor".Biochemical and Biophysical Research Communications.286 (5):958–963.doi:10.1006/bbrc.2001.5470.PMID11527393.
Bilban M, Ghaffari-Tabrizi N, Hintermann E, Bauer S, Molzer S, Zoratti C, et al. (March 2004). "Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts".Journal of Cell Science.117 (Pt 8):1319–1328.doi:10.1242/jcs.00971.PMID15020672.S2CID38523546.
"KiSS1-Derived Peptide Receptors".IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived fromthe original on 2016-02-06. Retrieved2007-11-02.
