Biology:KiSS1-derived peptide receptor
![]() Generic protein structure example |
The KiSS1-derived peptide receptor (also known as GPR54 or the Kisspeptin receptor) is a G protein-coupled receptor[1] which binds the peptide hormone kisspeptin (metastin).[2][3][4] Kisspeptin is encoded by the metastasis suppressor gene KISS1, which is expressed in a variety of endocrine and gonadal tissues.[5] Activation of the kisspeptin receptor is linked to the phospholipase C and inositol trisphosphate second messenger cascades inside the cell.[6]
Kisspeptins are neuropeptides synthesized in the hypothalamus and encoded by the KISS1 gene. The KISS1 gene encodes the G protein-coupled receptor 54 (known as KISS1R or GPR54) and plays a crucial role in regulating reproduction, pubertal maturation, and metabolic function.[7][8][9] KISS1 neurons located in the arcuate nucleus (ARC) of the mediobasal hypothalamus (MBH) project to GnRH neurons in the median eminence, which expresses KISS1R, to stimulate LH secretions in a pulsatile manner from the anterior pituitary to initiate ovulation/ pubertal maturation.[10][11][12] The KISS1 and KISS1R/GPR54 genes have been detected in the brain, pituitary, placenta, pancreas, liver, and small intestine.[10]
Function
Kisspeptin is involved in the regulation of endocrine function and the onset of puberty, with activation of the kisspeptin receptor triggering release of gonadotropin-releasing hormone (GnRH),[13][14] and release of kisspeptin itself being inhibited by oestradiol but enhanced by GnRH.[15] Reductions in kisspeptin levels with age may conversely be one of the reasons behind age-related declines in levels of other endocrine hormones such as luteinizing hormone.[16]
Clinical significance
Alterations in the KISS1/KISS1R signaling pathway have been linked to multiple physiological conditions, including metabolic and reproductive abnormalities.[17] A knockout model of GPR54/KISS1R in mice showed hypogonadism, and the mice failed to reach puberty.[17] The KISS1 gene has been stated to suppress the metastasis of malignant melanomas.[18] KISS1R signaling pathway has been characterized in the suppression of tumors and has anti-metastatic effects in several cancers, including breast cancer.[19][20]
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 the hypothalamic-pituitary axis and subsequent precocious puberty in rats and primates.[21][22] Mutations in the kisspeptin receptor KISS1R have resulted in isolated hypogonadotropic hypogonadism (IHH), characterized by delayed or absence of puberty [23]
Ligands
No non-peptide ligands for this receptor have yet been discovered, but as of 2009 both selective agonist and antagonist peptides are known.
Agonists
- Kisspeptin (kisspeptin-54, metastin)
- Kisspeptin-10 (112-121 C-terminal fragment)[24]
- KISS1-305
- MVT-602 (RVT-602, TAK-448)
- TAK-683
Antagonists
- Kisspeptin-10 analogues modified with amino substitutions[25]
- Kisspeptin-234
References
- ↑ "Discovery of a receptor related to the galanin receptors". FEBS Letters 446 (1): 103–107. March 1999. doi:10.1016/S0014-5793(99)00009-5. PMID 10100623.
- ↑ "Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor". Nature 411 (6837): 613–617. May 2001. doi:10.1038/35079135. PMID 11385580. Bibcode: 2001Natur.411..613O.
- ↑ "AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1". The Journal of Biological Chemistry 276 (31): 28969–28975. August 2001. doi:10.1074/jbc.M102743200. PMID 11387329.
- ↑ "The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54". The Journal of Biological Chemistry 276 (37): 34631–34636. September 2001. doi:10.1074/jbc.M104847200. PMID 11457843.
- ↑ "KiSS-1 and GPR54 at the pituitary level: overview and recent insights". Peptides 30 (1): 123–129. January 2009. doi:10.1016/j.peptides.2008.09.015. PMID 18948153.
- ↑ "Kisspeptin excites gonadotropin-releasing hormone neurons through a phospholipase C/calcium-dependent pathway regulating multiple ion channels". Endocrinology 149 (9): 4605–4614. September 2008. doi:10.1210/en.2008-0321. PMID 18483150.
- ↑ "The role of kisspeptin in the control of gonadotrophin secretion". Human Reproduction Update 15 (2): 203–212. 2008-11-05. doi:10.1093/humupd/dmn058. PMID 19109311.
- ↑ "Impaired kisspeptin signaling decreases metabolism and promotes glucose intolerance and obesity". The Journal of Clinical Investigation 124 (7): 3075–3079. July 2014. doi:10.1172/jci71075. PMID 24937427.
- ↑ "Glucagon regulates hepatic kisspeptin to impair insulin secretion". Cell Metabolism 19 (4): 667–681. April 2014. doi:10.1016/j.cmet.2014.03.005. PMID 24703698.
- ↑ 10.0 10.1 "The Role of Kiss1 Neurons As Integrators of Endocrine, Metabolic, and Environmental Factors in the Hypothalamic-Pituitary-Gonadal Axis". Frontiers in Endocrinology 9: 188. 2018-04-26. doi:10.3389/fendo.2018.00188. PMID 29755406.
- ↑ "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. October 2004. doi:10.1210/en.2004-0413. PMID 15242985.
- ↑ "Unaltered Hypothalamic Metabolic Gene Expression in Kiss1r Knockout Mice Despite Obesity and Reduced Energy Expenditure". Journal of Neuroendocrinology 28 (10). October 2016. doi:10.1111/jne.12430. PMID 27601011. PMC 5083214. https://escholarship.org/uc/item/09b2p5bs.
- ↑ "Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates". Proceedings of the National Academy of Sciences of the United States of America 102 (6): 2129–2134. February 2005. doi:10.1073/pnas.0409822102. PMID 15684075. Bibcode: 2005PNAS..102.2129S.
- ↑ "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. February 2006. doi:10.1210/en.2005-1261. PMID 16282350.
- ↑ "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. March 2008. doi:10.1111/j.1365-2826.2008.01653.x. PMID 18208554.
- ↑ "The excitatory peptide kisspeptin restores the luteinizing hormone surge and modulates amino acid neurotransmission in the medial preoptic area of middle-aged rats". Endocrinology 150 (8): 3699–3708. August 2009. doi:10.1210/en.2008-1667. PMID 19423763.
- ↑ 17.0 17.1 "The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system". Biochemical and Biophysical Research Communications 312 (4): 1357–1363. December 2003. doi:10.1016/j.bbrc.2003.11.066. PMID 14652023.
- ↑ "Expression of the metastasis suppressor gene KISS1 in uveal melanoma". Eye 22 (5): 707–711. May 2008. doi:10.1038/sj.eye.6703090. PMID 18219339.
- ↑ "Kisspeptin/KISS1R System in Breast Cancer". Journal of Cancer 4 (8): 653–661. September 2013. doi:10.7150/jca.7626. PMID 24155777.
- ↑ "KISS1/KISS1R and Breast Cancer: Metastasis Promoter". Seminars in Reproductive Medicine 37 (4): 197–206. July 2019. doi:10.1055/s-0039-3400968. PMID 31972865.
- ↑ "Advanced vaginal opening and precocious activation of the reproductive axis by KiSS-1 peptide, the endogenous ligand of GPR54". The Journal of Physiology 561 (Pt 2): 379–386. December 2004. doi:10.1113/jphysiol.2004.072298. PMID 15486019.
- ↑ "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. February 2006. doi:10.1210/en.2005-1261. PMID 16282350.
- ↑ "Mutations of the KISS1 gene in disorders of puberty". The Journal of Clinical Endocrinology and Metabolism 95 (5): 2276–2280. May 2010. doi:10.1210/jc.2009-2421. PMID 20237166.
- ↑ "Comparison of the effects of peripherally administered kisspeptins". Regulatory Peptides 152 (1–3): 95–100. January 2009. doi:10.1016/j.regpep.2008.10.001. PMID 18940206.
- ↑ "Discovery of potent kisspeptin antagonists delineate physiological mechanisms of gonadotropin regulation". The Journal of Neuroscience 29 (12): 3920–3929. March 2009. doi:10.1523/JNEUROSCI.5740-08.2009. PMID 19321788.
Further reading
- "GPR54 and puberty". Trends in Endocrinology and Metabolism 15 (9): 448–453. November 2004. doi:10.1016/j.tem.2004.09.008. PMID 15519892.
- "KiSS-1 and GPR54 as new players in gonadotropin regulation and puberty". Endocrine 26 (3): 277–284. April 2005. doi:10.1385/ENDO:26:3:277. PMID 16034182.
- "Metastin and its G protein-coupled receptor, GPR54: critical pathway modulating GnRH secretion". Frontiers in Neuroendocrinology 26 (3–4): 131–138. 2006. doi:10.1016/j.yfrne.2005.10.001. PMID 16309735.
- "GPR54 and kisspeptin in reproduction". Human Reproduction Update 12 (5): 631–639. 2006. doi:10.1093/humupd/dml023. PMID 16731583.
- "Human genetics of GPR54". Reviews in Endocrine & Metabolic Disorders 8 (1): 47–55. March 2007. doi:10.1007/s11154-007-9027-3. PMID 17334928.
- "Discovery of a receptor related to the galanin receptors". FEBS Letters 446 (1): 103–107. March 1999. doi:10.1016/S0014-5793(99)00009-5. PMID 10100623.
- "Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor". Nature 411 (6837): 613–617. May 2001. doi:10.1038/35079135. PMID 11385580. Bibcode: 2001Natur.411..613O.
- "AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1". The Journal of Biological Chemistry 276 (31): 28969–28975. August 2001. doi:10.1074/jbc.M102743200. PMID 11387329.
- "FMRFamide-related neuropeptides are agonists of the orphan G-protein-coupled receptor GPR54". Biochemical and Biophysical Research Communications 284 (5): 1189–1193. June 2001. doi:10.1006/bbrc.2001.5098. PMID 11414709.
- "The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54". The Journal of Biological Chemistry 276 (37): 34631–34636. September 2001. doi:10.1074/jbc.M104847200. PMID 11457843.
- "Metastin suppresses the motility and growth of CHO cells transfected with its receptor". Biochemical and Biophysical Research Communications 286 (5): 958–963. September 2001. doi:10.1006/bbrc.2001.5470. PMID 11527393.
- "Metastin receptor is overexpressed in papillary thyroid cancer and activates MAP kinase in thyroid cancer cells". The Journal of Clinical Endocrinology and Metabolism 87 (5): 2399. May 2002. doi:10.1210/jcem.87.5.8626. PMID 11994395.
- "Transcriptional expression of genes involved in cell invasion and migration by normal and tumoral trophoblast cells". The Journal of Clinical Endocrinology and Metabolism 87 (11): 5336–5339. November 2002. doi:10.1210/jc.2002-021093. PMID 12414911.
- "Autosomal recessive idiopathic hypogonadotropic hypogonadism: genetic analysis excludes mutations in the gonadotropin-releasing hormone (GnRH) and GnRH receptor genes". The Journal of Clinical Endocrinology and Metabolism 88 (6): 2730–2737. June 2003. doi:10.1210/jc.2002-021948. PMID 12788881.
- "Quantitative reverse transcriptase polymerase chain reaction analysis for KiSS-1 and orphan G-protein-coupled receptor (hOT7T175) gene expression in hepatocellular carcinoma". Journal of Cancer Research and Clinical Oncology 129 (9): 531–535. September 2003. doi:10.1007/s00432-003-0469-z. PMID 12898236.
- "Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54". Proceedings of the National Academy of Sciences of the United States of America 100 (19): 10972–10976. September 2003. doi:10.1073/pnas.1834399100. PMID 12944565. Bibcode: 2003PNAS..10010972D.
- "The GPR54 gene as a regulator of puberty". The New England Journal of Medicine 349 (17): 1614–1627. October 2003. doi:10.1056/NEJMoa035322. PMID 14573733.
- "Clinical significance of the loss of KiSS-1 and orphan G-protein-coupled receptor (hOT7T175) gene expression in esophageal squamous cell carcinoma". Clinical Cancer Research 10 (4): 1379–1383. February 2004. doi:10.1158/1078-0432.CCR-1519-02. PMID 14977840.
- "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. March 2004. doi:10.1242/jcs.00971. PMID 15020672.
External links
- "KiSS1-Derived Peptide Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1337.
- KISS1R+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
![]() | Original source: https://en.wikipedia.org/wiki/KiSS1-derived peptide receptor.
Read more |