KiSS1-derived peptide receptor

Last updated
KISS1R
Identifiers
Aliases KISS1R , AXOR12, CPPB1, GPR54, HH8, HOT7T175, KISS-1R, KiSS1-derived peptide receptor, KISS1 receptor
External IDs OMIM: 604161 MGI: 2148793 HomoloGene: 11411 GeneCards: KISS1R
Orthologs
SpeciesHumanMouse
Entrez

84634

114229

Ensembl

ENSG00000116014

ENSMUSG00000035773

UniProt

Q969F8

Q91V45

RefSeq (mRNA)

NM_032551

NM_053244
NM_001359010

RefSeq (protein)

NP_115940

NP_444474
NP_001345939

Location (UCSC) Chr 19: 0.92 – 0.92 Mb Chr 10: 79.75 – 79.76 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

The KiSS1-derived peptide receptor (also known as GPR54 or the Kisspeptin receptor) is a G protein-coupled receptor [5] which binds the peptide hormone kisspeptin (metastin). [6] [7] [8] Kisspeptin is encoded by the metastasis suppressor gene KISS1, which is expressed in a variety of endocrine and gonadal tissues. [9] Activation of the kisspeptin receptor is linked to the phospholipase C and inositol trisphosphate second messenger cascades inside the cell. [10]

Contents

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. [11] [12] [13] 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. [14] [15] [16] The KISS1 and KISS1R/GPR54 genes have been detected in the brain, pituitary, placenta, pancreas, liver, and small intestine. [14]

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), [17] [18] and release of kisspeptin itself being inhibited by oestradiol 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 as luteinizing hormone. [20]

Clinical significance

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 the hypothalamic-pituitary axis and subsequent precocious puberty in rats and primates. [25] [26] Mutations in the kisspeptin receptor KISS1R have resulted in isolated hypogonadotropic hypogonadism (IHH), characterized by delayed or absence of puberty [27]

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

Antagonists

Related Research Articles

<span class="mw-page-title-main">Corticotropin-releasing hormone</span> Mammalian protein found in humans

Corticotropin-releasing hormone (CRH) is a peptide hormone involved in stress responses. It is a releasing hormone that belongs to corticotropin-releasing factor family. In humans, it is encoded by the CRH gene. Its main function is the stimulation of the pituitary synthesis of adrenocorticotropic hormone (ACTH), as part of the hypothalamic–pituitary–adrenal axis.

<span class="mw-page-title-main">Gonadotropin-releasing hormone</span> Mammalian protein found in Homo sapiens

Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and released from GnRH neurons within the hypothalamus. The peptide belongs to gonadotropin-releasing hormone family. It constitutes the initial step in the hypothalamic–pituitary–gonadal axis.

In medicine, precocious puberty is puberty occurring at an unusually early age. In most cases, the process is normal in every aspect except the unusually early age and simply represents a variation of normal development. In a minority of children with precocious puberty, the early development is triggered by a disease such as a tumor or injury of the brain. Even when there is no disease, unusually early puberty can have adverse effects on social behavior and psychological development, can reduce adult height potential, and may shift some lifelong health risks. Central precocious puberty can be treated by suppressing the pituitary hormones that induce sex steroid production. The opposite condition is delayed puberty.

Gonadarche refers to the earliest gonadal changes of puberty. In response to pituitary gonadotropins, the ovaries in females and the testes in males begin to grow and increase the production of the sex steroids, especially estradiol and testosterone. The ovary and testis have receptors, follicle cells and leydig cells, respectively, where gonadotropins bind to stimulate the maturation of the gonads and secretion of estrogen and testosterone. Certain disorders can result in changes to timing or nature of these processes.

<span class="mw-page-title-main">Hypothalamic–pituitary–gonadal axis</span> Concept of regarding the hypothalamus, pituitary gland and gonadal glands as a single entity

The hypothalamic–pituitary–gonadal axis refers to the hypothalamus, pituitary gland, and gonadal glands as if these individual endocrine glands were a single entity. Because these glands often act in concert, physiologists and endocrinologists find it convenient and descriptive to speak of them as a single system.

Growth hormone–releasing hormone (GHRH), also known as somatocrinin or by several other names in its endogenous forms and as somatorelin (INN) in its pharmaceutical form, is a releasing hormone of growth hormone (GH). It is a 44-amino acid peptide hormone produced in the arcuate nucleus of the hypothalamus.

The gonadotropin-releasing hormone receptor (GnRHR), also known as the luteinizing hormone releasing hormone receptor (LHRHR), is a member of the seven-transmembrane, G-protein coupled receptor (GPCR) family. It is the receptor of gonadotropin-releasing hormone (GnRH). The GnRHR is expressed on the surface of pituitary gonadotrope cells as well as lymphocytes, breast, ovary, and prostate.

<span class="mw-page-title-main">Luteinizing hormone/choriogonadotropin receptor</span> Transmembrane receptor found in humans

The luteinizing hormone/choriogonadotropin receptor (LHCGR), also lutropin/choriogonadotropin receptor (LCGR) or luteinizing hormone receptor (LHR), is a transmembrane receptor found predominantly in the ovary and testis, but also many extragonadal organs such as the uterus and breasts. The receptor interacts with both luteinizing hormone (LH) and chorionic gonadotropins and represents a G protein-coupled receptor (GPCR). Its activation is necessary for the hormonal functioning during reproduction.

<span class="mw-page-title-main">Kisspeptin</span> Mammalian protein

Kisspeptins are proteins encoded by the KISS1 gene in humans. Kisspeptins are ligands of the G-protein coupled receptor, GPR54. Kiss1 was originally identified as a human metastasis suppressor gene that has the ability to suppress melanoma and breast cancer metastasis. Kisspeptin-GPR54 signaling has an important role in initiating secretion of gonadotropin-releasing hormone (GnRH) at puberty, the extent of which is an area of ongoing research. Gonadotropin-releasing hormone is released from the hypothalamus to act on the anterior pituitary triggering the release of luteinizing hormone (LH), and follicle stimulating hormone (FSH). These gonadotropic hormones lead to sexual maturation and gametogenesis. Disrupting GPR54 signaling can cause hypogonadotrophic hypogonadism in rodents and humans. The Kiss1 gene is located on chromosome 1. It is transcribed in the brain, adrenal gland, and pancreas.

<span class="mw-page-title-main">Neurokinin B</span> Chemical compound

Neurokinin B (NKB) belongs in the family of tachykinin peptides. Neurokinin B is implicated in a variety of human functions and pathways such as the secretion of gonadotropin-releasing hormone. Additionally, NKB is associated with pregnancy in females and maturation in young adults. Reproductive function is highly dependent on levels of both neurokinin B and also the G-protein coupled receptor ligand kisspeptin. The first NKB studies done attempted to resolve why high levels of the peptide may be implicated in pre-eclampsia during pregnancy. NKB, kisspeptin, and dynorphin together are found in the arcuate nucleus (ARC) known as the KNDy subpopulation. This subpopulation is targeted by many steroid hormones and works to form a network that feeds back to GnRH pulse generator.

<span class="mw-page-title-main">Growth hormone secretagogue receptor</span> Protein-coding gene in the species Homo sapiens

Growth hormone secretagogue receptor(GHS-R), also known as ghrelin receptor, is a G protein-coupled receptor that binds growth hormone secretagogues (GHSs), such as ghrelin, the "hunger hormone". The role of GHS-R is thought to be in regulating energy homeostasis and body weight. In the brain, they are most highly expressed in the hypothalamus, specifically the ventromedial nucleus and arcuate nucleus. GSH-Rs are also expressed in other areas of the brain, including the ventral tegmental area, hippocampus, and substantia nigra. Outside the central nervous system, too, GSH-Rs are also found in the liver, in skeletal muscle, and even in the heart.

<span class="mw-page-title-main">GNRHR</span> Protein-coding gene in the species Homo sapiens

Gonadotropin-releasing hormone receptor is a protein that in humans is encoded by the GNRHR gene.

<span class="mw-page-title-main">Corticotropin-releasing hormone receptor 2</span> Protein found in humans

Corticotropin-releasing hormone receptor 2 (CRHR2) is a protein, also known by the IUPHAR-recommended name CRF2, that is encoded by the CRHR2 gene and occurs on the surfaces of some mammalian cells. CRF2 receptors are type 2 G protein-coupled receptors for corticotropin-releasing hormone (CRH) that are resident in the plasma membranes of hormone-sensitive cells. CRH, a peptide of 41 amino acids synthesized in the hypothalamus, is the principal neuroregulator of the hypothalamic-pituitary-adrenal axis, signaling via guanine nucleotide-binding proteins (G proteins) and downstream effectors such as adenylate cyclase. The CRF2 receptor is a multi-pass membrane protein with a transmembrane domain composed of seven helices arranged in a V-shape. CRF2 receptors are activated by two structurally similar peptides, urocortin II, and urocortin III, as well as CRH.

<span class="mw-page-title-main">Parathyroid hormone 2 receptor</span> Protein-coding gene in the species Homo sapiens

Parathyroid hormone 2 receptor is a protein that in humans is encoded by the PTH2R gene.

<span class="mw-page-title-main">Relaxin/insulin-like family peptide receptor 1</span> Protein-coding gene in the species Homo sapiens

Relaxin/insulin-like family peptide receptor 1, also known as RXFP1, is a human G protein coupled receptor that is one of the relaxin receptors. It is a rhodopsin-like GPCR which is unusual in this class as it contains a large extracellular binding and signalling domain. Some reports suggest that RXFP1 forms homodimers, however the most recent evidence indicates that relaxin binds a non-homodimer of RXFP1.

<span class="mw-page-title-main">GNRHR2</span> Pseudogene in the species Homo sapiens

Putative gonadotropin-releasing hormone II receptor is a protein that in humans is encoded by the GNRHR2 gene.

Progonadoliberin-2 is a protein that in humans is encoded by the GNRH2 gene.

Hypogonadotropic hypogonadism (HH), is due to problems with either the hypothalamus or pituitary gland affecting the hypothalamic-pituitary-gonadal axis. Hypothalamic disorders result from a deficiency in the release of gonadotropic releasing hormone (GnRH), while pituitary gland disorders are due to a deficiency in the release of gonadotropins from the anterior pituitary. GnRH is the central regulator in reproductive function and sexual development via the HPG axis. GnRH is released by GnRH neurons, which are hypothalamic neuroendocrine cells, into the hypophyseal portal system acting on gonadotrophs in the anterior pituitary. The release of gonadotropins, LH and FSH, act on the gonads for the development and maintenance of proper adult reproductive physiology. LH acts on Leydig cells in the male testes and theca cells in the female. FSH acts on Sertoli cells in the male and follicular cells in the female. Combined this causes the secretion of gonadal sex steroids and the initiation of folliculogenesis and spermatogenesis. The production of sex steroids forms a negative feedback loop acting on both the anterior pituitary and hypothalamus causing a pulsatile secretion of GnRH. GnRH neurons lack sex steroid receptors and mediators such as kisspeptin stimulate GnRH neurons for pulsatile secretion of GnRH.

Kisspeptin, neurokinin B, and dynorphin (KNDy) neurons are neurons in the hypothalamus of the brain that are central to the hormonal control of reproduction.

Gonadotropin-inhibitory hormone (GnIH) is a RFamide-related peptide coded by the NPVF gene in mammals.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000116014 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000035773 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Lee DK, Nguyen T, O'Neill GP, Cheng R, Liu Y, Howard AD, et al. (March 1999). "Discovery of a receptor related to the galanin receptors". FEBS Letters. 446 (1): 103–107. doi:10.1016/S0014-5793(99)00009-5. PMID   10100623. S2CID   38910830.
  6. ↑ Ohtaki T, Shintani Y, Honda S, Matsumoto H, Hori A, Kanehashi K, et al. (May 2001). "Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor". Nature. 411 (6837): 613–617. Bibcode:2001Natur.411..613O. doi:10.1038/35079135. PMID   11385580. S2CID   205017670.
  7. ↑ Muir AI, Chamberlain L, Elshourbagy NA, Michalovich D, Moore DJ, Calamari A, et al. (August 2001). "AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1". The Journal of Biological Chemistry. 276 (31): 28969–28975. doi: 10.1074/jbc.M102743200 . PMID   11387329.
  8. ↑ Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le Poul E, et al. (September 2001). "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. doi: 10.1074/jbc.M104847200 . PMID   11457843.
  9. ↑ Richard N, Corvaisier S, Camacho E, Kottler ML (January 2009). "KiSS-1 and GPR54 at the pituitary level: overview and recent insights". Peptides. 30 (1): 123–129. doi:10.1016/j.peptides.2008.09.015. PMID   18948153. S2CID   22875820.
  10. ↑ Liu X, Lee K, Herbison AE (September 2008). "Kisspeptin excites gonadotropin-releasing hormone neurons through a phospholipase C/calcium-dependent pathway regulating multiple ion channels". Endocrinology. 149 (9): 4605–4614. doi:10.1210/en.2008-0321. PMC   6116891 . PMID   18483150.
  11. ↑ Roseweir AK, Millar RP (2008-11-05). "The role of kisspeptin in the control of gonadotrophin secretion". Human Reproduction Update. 15 (2): 203–212. doi: 10.1093/humupd/dmn058 . PMID   19109311.
  12. ↑ Tolson KP, Garcia C, Yen S, Simonds S, Stefanidis A, Lawrence A, et al. (July 2014). "Impaired kisspeptin signaling decreases metabolism and promotes glucose intolerance and obesity". The Journal of Clinical Investigation. 124 (7): 3075–3079. doi:10.1172/jci71075. PMC   4071390 . PMID   24937427.
  13. ↑ Song WJ, Mondal P, Wolfe A, Alonso LC, Stamateris R, Ong BW, et al. (April 2014). "Glucagon regulates hepatic kisspeptin to impair insulin secretion". Cell Metabolism. 19 (4): 667–681. doi:10.1016/j.cmet.2014.03.005. PMC   4058888 . PMID   24703698.
  14. 1 2 Yeo SH, Colledge WH (2018-04-26). "The Role of Kiss1 Neurons As Integrators of Endocrine, Metabolic, and Environmental Factors in the Hypothalamic-Pituitary-Gonadal Axis". Frontiers in Endocrinology. 9: 188. doi: 10.3389/fendo.2018.00188 . PMC   5932150 . PMID   29755406.
  15. ↑ 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. PMID   15242985. S2CID   14817781.
  16. ↑ De Bond JP, Tolson KP, Nasamran C, Kauffman AS, Smith JT (October 2016). "Unaltered Hypothalamic Metabolic Gene Expression in Kiss1r Knockout Mice Despite Obesity and Reduced Energy Expenditure". Journal of Neuroendocrinology. 28 (10). doi:10.1111/jne.12430. PMC   5083214 . PMID   27601011. S2CID   3542864.
  17. ↑ Shahab M, Mastronardi C, Seminara SB, Crowley WF, Ojeda SR, Plant TM (February 2005). "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. Bibcode:2005PNAS..102.2129S. doi: 10.1073/pnas.0409822102 . PMC   548549 . PMID   15684075.
  18. ↑ 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. PMID   16282350.
  19. ↑ 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. PMID   18208554. S2CID   205345039.
  20. ↑ Neal-Perry G, Lebesgue D, Lederman M, Shu J, Zeevalk GD, Etgen AM (August 2009). "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. doi:10.1210/en.2008-1667. PMC   2717872 . PMID   19423763.
  21. 1 2 Funes 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. PMID   14652023.
  22. ↑ Martins CM, Fernandes BF, Antecka E, Di Cesare S, Mansure JJ, Marshall JC, Burnier MN (May 2008). "Expression of the metastasis suppressor gene KISS1 in uveal melanoma". Eye. 22 (5): 707–711. doi: 10.1038/sj.eye.6703090 . PMID   18219339.
  23. ↑ Cvetković D, Babwah AV, Bhattacharya M (September 2013). "Kisspeptin/KISS1R System in Breast Cancer". Journal of Cancer. 4 (8): 653–661. doi:10.7150/jca.7626. PMC   3805993 . PMID   24155777.
  24. ↑ 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. PMID   31972865. S2CID   210883188.
  25. ↑ Navarro VM, Fernández-Fernández R, Castellano JM, Roa J, Mayen A, Barreiro ML, et al. (December 2004). "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. doi:10.1113/jphysiol.2004.072298. PMC   1665361 . PMID   15486019.
  26. ↑ 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. PMID   16282350.
  27. ↑ Silveira LG, Noel SD, Silveira-Neto AP, Abreu AP, Brito VN, Santos MG, et al. (May 2010). "Mutations of the KISS1 gene in disorders of puberty". The Journal of Clinical Endocrinology and Metabolism. 95 (5): 2276–2280. doi:10.1210/jc.2009-2421. PMC   2869552 . PMID   20237166.
  28. ↑ Mikkelsen JD, Bentsen AH, Ansel L, Simonneaux V, Juul A (January 2009). "Comparison of the effects of peripherally administered kisspeptins". Regulatory Peptides. 152 (1–3): 95–100. doi:10.1016/j.regpep.2008.10.001. PMID   18940206. S2CID   6587724.
  29. ↑ Roseweir AK, Kauffman AS, Smith JT, Guerriero KA, Morgan K, Pielecka-Fortuna J, et al. (March 2009). "Discovery of potent kisspeptin antagonists delineate physiological mechanisms of gonadotropin regulation". The Journal of Neuroscience. 29 (12): 3920–3929. doi:10.1523/JNEUROSCI.5740-08.2009. PMC   3035813 . PMID   19321788.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.