Kisspeptins: A multifunctional peptide system with a role in reproduction, cancer and the cardiovascular system

British Journal of Pharmacology

Volumn 151, Issue 8, 2007, Pages 1143-1153

  Mead, E J ^a   Maguire, J J ^a   Kuc, R E ^a   Davenport, A P ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

Cardiovascular; GPR54; KiSS 1; KISS1; Kisspeptin; Metastasis; Orphan G protein coupled receptor; Placentation; Puberty; Vasoconstrictor

Indexed keywords

ALANINE; CYCLIC AMP; DEXTRO AMINO ACID; G PROTEIN COUPLED RECEPTOR 54; GELATINASE A; GELATINASE B; GONADORELIN; KISSPEPTIN; MATRIX METALLOPROTEINASE; PEPTIDE;

AMINO ACID SEQUENCE; ANGIOGENESIS; ATHEROSCLEROSIS; BRAIN NERVE CELL; CALCIUM CELL LEVEL; CANCER; CARDIOVASCULAR DISEASE; CARDIOVASCULAR SYSTEM; CELL ADHESION; CELL MOTILITY; CORRELATION ANALYSIS; CYTOSKELETON; DIABETES MELLITUS; DOWN REGULATION; DOWNSTREAM PROCESSING; ESTRUS CYCLE; GENE MUTATION; GENETIC LINKAGE; HUMAN; HYPOGONADOTROPIC HYPOGONADISM; INHIBITION KINETICS; KNOCKOUT MOUSE; METASTASIS; MICROARRAY ANALYSIS; NONHUMAN; OBESITY; PLACENTA; POLYMERASE CHAIN REACTION; PREGNANCY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PUBERTY; REPRODUCTION; REVIEW; SIGNAL TRANSDUCTION; TROPHOBLAST; VASOCONSTRICTION;

CARDIOVASCULAR SYSTEM; DRUG DELIVERY SYSTEMS; HUMANS; NEOPLASM METASTASIS; NEOPLASMS; RECEPTORS, G-PROTEIN-COUPLED; REPRODUCTION; TUMOR SUPPRESSOR PROTEINS;

EID: 34547910242     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1038/sj.bjp.0707295     Document Type: Review

References (77)

1. Aparicio S (2005). Kisspeptins and GPR54 - the new biology of the mammalian GnRH axis. Cell Metab 1: 293-296.
2. Becker JA, Mirjolet JF, Bernard J, Burgeon E, Simons MJ, Vassart G et al. (2005). Activation of GPR54 promotes cell cycle arrest and apoptosis of human tumor cells through a specific transcriptional program not shared by other Gq-coupled receptors. Biochem Biophys Res Commun 326: 677-686.
3. Bilban M, Ghaffari-Tabrizi N, Hintermann E, Bauer S, Molzer S, Zoratti C et al. (2004). Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts. J Cell Sci 117: 1319-1328.
4. Castellano JM, Gaytan M, Roa J, Vigo E, Navarro VM, Bellido C et al. (2006a). Expression of KiSS-1 in rat ovary: putative local regulator of ovulation? Endocrinology 147: 4852-4862.
5. Castellano JM, Navarro VM, Fernandez-Fernandez R, Nogueiras R, Tovar S, Roa J et al. (2005). Changes in hypothalamic KiSS-1 system and restoration of pubertal activation of the reproductive axis by kisspeptin in undernutrition. Endocrinology 146: 3917-3925.
6. Castellano JM, Navarro VM, Fernandez-Fernandez R, Roa J, Vigo E, Pineda R et al. (2006b). Expression of hypothalamic KiSS-1 system and rescue of defective gonadotropic responses by kisspeptin in streptozotocin-induced diabetic male rats. Diabetes 55: 2602-2610.
7. Clarkson J, Herbison AE (2006). Postnatal development of kisspeptin neurons in mouse hypothalamus; sexual dimorphism and projections to gonadotropin-releasing hormone neurons. Endocrinology 147: 5817-5825.
8. Clements MK, McDonald TP, Wang R, Xie G, O'Dowd BF, George SR et al. (2001). FMRFamide-related neuropeptides are agonists of the orphan G-protein-coupled receptor GPR54. Biochem Biophys Res Commun 284: 1189-1193.
9. Davenport AP, Mead EJ (2005). KiSS1 - derived peptide receptor. IUPHAR Receptor database (http://www.iuphar-db.org/GPCR/ReceptorDisplayForward? receptorID=2989 ).
10. de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E (2003). Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci USA 100: 10972-10976.
11. Dhar DK, Naora H, Kubota H, Maruyama R, Yoshimura H, Tonomoto Y et al. (2004). Downregulation of KiSS-1 expression is responsible for tumor invasion and worse prognosis in gastric carcinoma. Int J Cancer 111: 868-872.
12. Dhillo WS, Chaudhri OB, Patterson M, Thompson EL, Murphy KG, Badman MK et al. (2005). Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. J Clin Endocrinol Metab 90: 6609-6615.
13. Dungan HM, Clifton DK, Steiner RA (2006). Minireview: kisspeptin neurons as central processors in the regulation of gonadotropin-releasing hormone secretion. Endocrinology 147: 1154-1158.
14. Farina A, Sekizawa A, Purwosunu Y, Rizzo N, Banzola I, Concu M et al. (2006). Quantitative distribution of a panel of circulating mRNA in preeclampsia versus controls. Prenat Diagn 26: 1115-1120.
15. Foord SM, Bonner TI, Neubig RR, Rosser EM, Pin JP, Davenport AP et al. (2005). International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev 57: 279-288.
16. Funes S, Hedrick JA, Vassileva G, Markowitz L, Abbondanzo S, Golovko A et al. (2003). The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system. Biochem Biophys Res Commun 312: 1357-1363.
17. Goldberg SF, Miele ME, Hatta N, Takata M, Paquette-Straub C, Freedman LP et al. (2003). Melanoma metastasis suppression by chromosome 6: evidence for a pathway regulated by CRSP3 and TXNIP. Cancer Res 63: 432-440.
18. Gottsch ML, Cunningham MJ, Smith JT, Popa SM, Acohido BV, Crowley WF et al. (2004). A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology 145: 4073-4077.
19. Han SK, Gottsch ML, Lee KJ, Popa SM, Smith JT, Jakawich SK et al. (2005). Activation of gonadotropin-releasing hormone neurons by kisspeptin as a neuroendocrine switch for the onset of puberty. J Neurosci 25: 11349-11356.
20. Harms JF, Welch DR, Miele ME (2003). KISS1 metastasis suppression and emergent pathways. Clin Exp Metastasis 20: 11-18.
21. Hauge-Evans AC, Richardson CC, Milne HM, Christie MR, Persaud SJ, Jones PM (2006). A role for kisspeptin in islet function. Diabetologia 49: 2131-2135.
22. Hesling C, D'Incan M, Mansard S, Franck F, Corbin-Duval A, Chevenet C et al. (2004). In vivo and in situ modulation of the expression of genes involved in metastasis and angiogenesis in a patient treated with topical imiquimod for melanoma skin metastases. Br J Dermatol 150: 761-767.
23. Hori A, Honda S, Asada M, Ohtaki T, Oda K, Watanabe T et al. (2001). Metastin suppresses the motility and growth of CHO cells transfected with its receptor. Biochem Biophys Res Commun 286: 958-963.
24. Horikoshi Y, Matsumoto H, Takatsu Y, Ohtaki T, Kitada C, Usuki S et al. (2003). Dramatic elevation of plasma metastin concentrations in human pregnancy: metastin as a novel placenta-derived hormone in humans. J Clin Endocrinol Metab 88: 914-919.
25. Ikeguchi M, Hirooka Y, Kaibara N (2003). Quantitative reverse transcriptase polymerase chain reaction analysis for KiSS-1 and orphan G-protein-coupled receptor (hOT7T175) gene expression in hepatocellular carcinoma. J Cancer Res Clin Oncol 129: 531-535.
26. Ikeguchi M, Yamaguchi K, Kaibara N (2004). Clinical significance of the loss of KiSS-1 and orphan G-protein-coupled receptor (hOT7T175) gene expression in esophageal squamous cell carcinoma. Clin Cancer Res 10: 1379-1383.
27. International Human Genome Sequencing Consortium (2004). Finishing the euchromatic sequence of the human genome. Nature 431: 931-945.
28. Irwig MS, Fraley GS, Smith JT, Acohido BV, Popa SM, Cunningham MJ et al. (2005). Kisspeptin activation of gonadotropin releasing hormone neurons and regulation of KiSS-1 mRNA in the male rat. Neuroendocrinology 80: 264-272.
29. Janneau JL, Maldonado-Estrada J, Tachdjian G, Miran I, Motte N, Saulnier P et al. (2002). Transcriptional expression of genes involved in cell invasion and migration by normal and tumoral trophoblast cells. J Clin Endocrinol Metab 87: 5336-5339.
30. Jiang T, Zhang SL, Lin B, Meng LR, Gao H (2005). Expression and clinical significance of KISS-1 and GPR54 mRNA in endometrial carcinoma. Zhonghua Zhong Liu Za Zhi 27: 229-231.
31. Kauffman AS, Gottsch ML, Roa J, Byquist AC, Crown A, Clifton DK et al. (2007). Sexual differentiation of Kiss1 gene expression in the brain of the rat. Endocrinology 184: 1774-1783.
32. Kinoshita M, Tsukamura H, Adachi S, Matsui H, Uenoyama Y, Iwata K et al. (2005). Involvement of central metastin in the regulation of preovulatory luteinizing hormone surge and estrous cyclicity in female rats. Endocrinology 146: 4431-4436.
33. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K (1999). Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402: 656-660.
34. Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le Poul E et al. (2001). The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem 276: 34631-34636.
35. Lee DK, Nguyen T, O'Neill GP, Cheng R, Liu Y, Howard AD et al. (1999). Discovery of a receptor related to the galanin receptors. FEBS Lett 446: 103-107.
36. Lee JH, Miele ME, Hicks DJ, Phillips KK, Trent JM, Weissman BE et al. (1996). KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J Natl Cancer Inst 88: 1731-1737.
37. Lee JH, Welch DR (1997). Suppression of metastasis in human breast carcinoma MDA-MB-435 cells after transfection with the metastasis suppressor gene, KiSS-1. Cancer Res 57: 2384-2387.
38. MacDonald MLE (2004). Mutations in a G protein-coupled receptor cause hypogonadotrophic hypogonadism in humans and mice. Clin Genet 65: 177-182.
39. Maguire JJ, Davenport AP (2005). Regulation of vascular reactivity by established and emerging GPCRs. Trends Pharmacol Sci 26: 448-454.
40. Martini AC, Fernandez-Fernandez R, Tovar S, Navarro VM, Vigo E, Vazquez MJ et al. (2006). Comparative analysis of the effects of ghrelin and unacylated ghrelin on luteinizing hormone secretion in male rats. Endocrinology 147: 2374-2382.
41. Masui T, Doi R, Mori T, Toyoda E, Koizumi M, Kami K et al. (2004). Metastin and its variant forms suppress migration of pancreatic cancer cells. Biochem Biophys Res Commun 315: 85-92.
42. Matsui H, Takatsu Y, Kumano S, Matsumoto H, Ohtaki T (2004). Peripheral administration of metastin induces marked gonadotropin release and ovulation in the rat. Biochem Biophys Res Commun 320: 383-388.
43. Mead EJ, Maguire JJ, Kuc RE, Davenport AP (2006). Kisspeptins are novel potent vasoconstrictors in humans, with a discrete localization of their receptor GPR54, to atherosclerosis prone vessels. Endocrinology 148: 140-147.
44. Messager S, Chatzidaki EE, Ma D, Hendrick AG, Zahn D, Dixon J et al. (2005). Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc Natl Acad Sci USA 102: 1761-1766.
45. Miele ME, Robertson G, Lee JH, Coleman A, McGary CT, Fisher PB et al. (1996). Metastasis suppressed, but tumorigenicity and local invasiveness unaffected, in the human melanoma cell line MelJuSo after introduction of human chromosomes 1 or 6. Mol Carcinog 15: 284-299.
46. Mitchell DC, Abdelrahim M, Weng J, Stafford LJ, Safe S, Bar-Eli M et al. (2006). Regulation of KiSS-1 metastasis suppressor gene expression in breast cancer cells by direct interaction of transcription factors activator protein-2alpha and specificity protein-1. J Biol Chem 281: 51-58.
47. Muir AI, Chamberlain L, Elshourbagy NA, Michalovich D, Moore DJ, Calamari A et al. (2001). AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1. J Biol Chem 276: 28969-28975.
48. Mullins LJ, Mullins JJ (2004). Large transgenes reveal their secrets. Focus on 'differential expression of the closely linked KISS1, REN, and FLJ10761 genes in transgenic mice'. Physiol Genomics 17: 1-3.
49. Navarro VM, Castellano JM, Fernandez-Fernandez R, Barreiro ML, Roa J, Sanchez-Criado JE et al. (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: 4565-4574.
50. Ohtaki T, Shintani Y, Honda S, Matsumoto H, Hori A, Kanehashi K et al. (2001). Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature 411: 613-617.
51. Orsini MJ, Klein MA, Beavers MP, Connolly PJ, Middleton SA, Mayo KH (2007). Metastin (KiSS-1) mimetics identified from peptide structure-activity relationship-derived pharmacophores and directed small molecule database screening. J Med Chem 50: 462-471.
52. Panidis D, Rousso D, Koliakos G, Kourtis A, Katsikis I, Farmakiotis D et al. (2006). Plasma metastin levels are negatively correlated with insulin resistance and free androgens in women with polycystic ovary syndrome. Fertil Steril 85: 1778-1783.
53. Qiao C, Wang CH, Shang T, Lin QD (2005). Clinical significance of KiSS-1 and matrix metalloproteinase-9 expression in trophoblasts of women with preeclampsia and their relation to perinatal outcome of neonates. Zhonghua Fu Chan Ke Za Zhi 40: 585-590.
54. Revel FG, Saboureau M, Masson-Pevet M, Pevet P, Simonneaux V, Horvath TL et al. (2006). Kiss-1 is a likely candidate for the photoperiodic control of reproduction. Chronobiol Int 23: 277-287.
55. Ringel MD, Hardy E, Bernet VJ, Burch HB, Schuppert F, Burman KD et al. (2002). Metastin receptor is overexpressed in papillary thyroid cancer and activates MAP kinase in thyroid cancer cells. J Clin Endocrinol Metab 87: 2399.
56. Roa J, Vigo E, Castellano JM, Navarro VM, Fernandez-Fernandez R, Casanueva FF et al. (2006). Hypothalamic expression of KiSS-1 system and gonadotropin-releasing effects of kisspeptin in different reproductive states of the female Rat. Endocrinology 147: 2864-2878.
57. Sanchez-Carbayo M, Belbin TJ, Scotlandi K, Prystowsky M, Baldini N, Childs G et al. (2003a). Expression profiling of osteosarcoma cells transfected with MDR1 and NEO genes: regulation of cell adhesion, apoptosis, and tumor suppression-related genes. Lab Invest 83: 507-517.
58. Sanchez-Carbayo M, Capodieci P, Cordon-Cardo C (2003b). Tumor suppressor role of KiSS-1 in bladder cancer: loss of KiSS-1 expression is associated with bladder cancer progression and clinical outcome. Am J Pathol 162: 609-617.
59. Seminara SB, Dipietro MJ, Ramaswamy S, Crowley Jr WF, Plant TM (2006). Continuous human metastin 45-54 infusion desensitizes G protein-coupled receptor 54-induced gonadotropin-releasing hormone release monitored indirectly in the juvenile male Rhesus monkey (Macaca mulatta): a finding with therapeutic implications. Endocrinology 147: 2122-2126.
60. Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno Jr JS, Shagoury JK et al. (2003). The GPR54 gene as a regulator of puberty. N Engl J Med 349: 1614-1627.
61. Semple RK, Achermann JC, Ellery J, Farooqi IS, Karet FE, Stanhope RG et al. (2005). Two novel missense mutations in G protein-coupled receptor 54 in a patient with hypogonadotropic hypogonadism. J Clin Endocrinol Metab 90: 1849-1855.
62. Shahab M, Mastronardi C, Seminara SB, Crowley WF, Ojeda SR, Plant TM (2005). Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates. Proc Natl Acad Sci USA 102: 2129-2134.
63. Shirasaki F, Takata M, Hatta N, Takehara K (2001). Loss of expression of the metastasis suppressor gene KiSS1 during melanoma progression and its association with LOH of chromosome 6q16.3-q23. Cancer Res 61: 7422-7425.
64. Smith JT, Acohido BV, Clifton DK, Steiner RA (2006a). KiSS-1 neurones are direct targets for leptin in the ob/ob mouse. J Neuroendocrinol 18: 298-303.
65. Smith JT, Clay CM, Caraty A, Clarke IJ (2007). KiSS-1 messenger ribonucleic acid expression in the hypothalamus of the ewe is regulated by sex steroids and season. Endocrinology 148: 1150-1157.
66. Smith JT, Cunningham MJ, Rissman EF, Clifton DK, Steiner RA (2005a). Regulation of Kiss1 gene expression in the brain of the female mouse. Endocrinology 146: 3686-3692.
67. Smith JT, Dungan HM, Stoll EA, Gottsch ML, Braun RE, Eacker SM et al. (2005b). Differential regulation of KiSS-1 mRNA expression by sex steroids in the brain of the male mouse. Endocrinology 146: 2976-2984.
68. Smith JT, Popa SM, Clifton DK, Hoffman GE, Steiner RA (2006b). Kiss1 neurons in the forebrain as central processors for generating the preovulatory luteinizing hormone surge. J Neurosci 26: 6687-6694.
69. Takino T, Koshikawa N, Miyamori H, Tanaka M, Sasaki T, Okada Y et al. (2003). Cleavage of metastasis suppressor gene product KiSS-1 protein/metastin by matrix metalloproteinases. Oncogene 22: 4617-4626.
70. Thompson EL, Murphy KG, Patterson M, Bewick GA, Stamp GW, Curtis AE et al. (2006). Chronic subcutaneous administration of kisspeptin-54 causes testicular degeneration in adult male rats. Am J Physiol Endocrinol Metab 291: E1074-E1082.
71. Thompson EL, Patterson M, Murphy KG, Smith KL, Dhillo WS, Todd JF et al. (2004). Central and peripheral administration of kisspeptin-10 stimulates the hypothalamic-pituitary-gonadal axis. J Neuroendocrinol 16: 850-858.
72. Tomita K, Narumi T, Niida A, Oishi S, Ohno H, Fujii N (2007). Fmoc-based solid-phase synthesis of GPR54-agonistic pentapeptide derivatives containing alkene- and fluoroalkene-dipeptide isosteres. Biopolymers 14: 7595-7603.
73. Wintermantel TM, Campbell RE, Porteous R, Bock D, Grone H, Todman MG et al. (2006). Definition of estrogen receptor pathway critical for estrogen positive feedback to gonadotropin-releasing hormone neurons and fertility. Neuron 52: 271-280.
74. Wise A, Gearing K, Rees S (2002). Target validation of G-protein coupled receptors. Drug Discov Today 7: 235-246.
75. Wisotzkey JD, Neff M, Pandelidis S (1997). Differential expression of the KISS-1 metastasis suppressor gene in colon cancer. Am J Pathol 151: ST17.
76. Yamada S, Uenoyama Y, Kinoshita M, Iwata K, Takase K, Matsui H et al. (2007). Inhibition of metastin (Kisspeptin-54)-GPR 54 signaling in the arcuate nucleus-median eminence region during lactation in rats. Endocrinology 148: 2226-2232.
77. Yan C, Wang H, Boyd DD (2001). KiSS-1 represses 92-kDa type IV collagenase expression by down-regulating NF-kappa B binding to the promoter as a consequence of Ikappa Balpha-induced block of p65/p50 nuclear translocation. J Biol Chem 276: 1164-1172.