Kisspeptin 10 mg

▎ Kisspeptin Structure

▎ Kisspeptin Kev Tshawb Fawb

Kev tshawb fawb keeb kwm ntawm Kisspeptin yog dab tsi?  

Nyob rau hauv lub xyoo pua 20th lig, nrog rau kev nce qib hauv kev tshawb fawb ntawm cov qog metastasis suppressor noob, cov kws tshawb fawb tau tshawb pom KiSS-1 gene hauv melanoma hlwb siv kev hloov pauv hybridization hauv xyoo 1996. Hauv xyoo 1999, nas G protein-coupled receptor GPR54 tau txheeb xyuas, thiab hauv 2001 cov khoom lag luam paub tseeb tias KiSS1. ligand rau GPR54, hu ua Kisspeptin. Thaum xub thawj tau sau tseg rau nws cov qog metastasis-suppressive zog, qhov no neuropeptide tom qab tau pom los ua lub luag haujlwm tseem ceeb ntawm kev tswj hwm ntawm hypothalamic-pituitary-gonadal axis, ua si lub luag haujlwm tseem ceeb hauv kev tswj hwm neuroendocrine ntawm vertebrate reproductive txoj kev loj hlob. Nws kuj koom nrog ntau yam txheej txheem physiological xws li kev xeeb tub, kev tswj kom zoo, kev loj hlob metabolism, thiab kev noj zaub mov. Qhov kev tshawb pom thiab kev ua haujlwm ntawm Kisspeptin muab lub hauv paus tseem ceeb rau kev tshawb nrhiav cov txheej txheem tswj hwm neuroendocrine thiab kho cov kab mob ntsig txog.  

Lub mechanism ntawm kev txiav txim ntawm Kisspeptin yog dab tsi?  

Reproductive Regulatory Mechanisms  

Kev tswj hwm ntawm Hypothalamic-Pituitary-Gonadal (HPG) Axis: Kisspeptin plays lub luag haujlwm tseem ceeb hauv kev tswj kev ua me nyuam, feem ntau los ntawm kev hloov kho ntawm HPG axis. Hauv cov tsiaj txhu, Kisspeptin txhawb kev tso tawm ntawm gonadotropin-tso hormone (GnRH). Tshwj xeeb, Kisspeptin qhib lub pulsatile secretion ntawm GnRH hlwb ntawm G protein-coupled mechanisms los ntawm nws cov receptor GPR54. Piv txwv li, thaum lub sij hawm puberty pib, nce kev ua haujlwm ntawm hypothalamic Kisspeptin neurons txhawb nqa GnRH secretion, uas ua rau lub caj pas pituitary secrete gonadotropins (xws li follicle-stimulating hormone FSH thiab luteinizing hormone LH). Cov tshuaj hormones no ua rau gonads los txhawb kev loj hlob ntawm gonadal thiab kev sib deev hormone secretion, yog li pib kev loj hlob ntawm pubertal ^[1] .  

Direct Effects on Gonads: Ntxiv nrog rau kev tswj tsis ncaj ntawm kev yug me nyuam los ntawm HPG axis, Kisspeptin kuj muaj kev cuam tshuam ncaj qha rau gonads. Kev tshawb fawb ntawm oocytes los ntawm anestrous Tan yaj, piv txwv li, tau pom tias Kisspeptin txhim kho qhov kev loj hlob hauv vitro ntawm Tan yaj oocytes thiab txhawb oocyte maturation los ntawm upregulating noob qhia. Qhov no qhia tias Kisspeptin tuaj yeem koom ncaj qha rau hauv kev tswj follicular kev loj hlob hauv gonads.  

Kisspeptin's mechanism ntawm kev txiav txim yog dab tsi?

Kev cuam tshuam nrog Lwm Cov Neuropeptides: Hauv hypothalamic arcuate nucleus, muaj chav kawm ntawm Kisspeptin neurons uas co-express glutamate, neurokinin B (NKB), thiab dynorphin (Dyn). Cov neurons no muaj kev sib cuam tshuam synchronous ua haujlwm los tsav pulsatile hormone secretion ^[2] . Cov kev tshawb fawb hauv cov nas poj niam tau pom tias kev sib koom ua ke ntawm ARN^{KISS} cov neurons siab heev nyob ntawm glutamate kis ntawm AMPA receptors thiab neurokinin B kis tau tus mob, thaum inhibition ntawm NMDA receptors thiab κ-opioid receptors tsis muaj kev cuam tshuam rau synchronization tus nqi ^[3] . Nyob rau hauv cov txiv neej nas, synchronization ntawm ARN^{KISS} neurons tshwm sim los ntawm ze li ntawm random burst network kev ua si nyob rau hauv cov pej xeem, tseem ceeb nyob rau hauv lub zos glutamate-AMPA signaling, nrog neurokinin B txhim kho glutamate-induced synchronization, thaum dynorphin-κ-opioid suab nyob rau hauv lub network ua syncronization pib. Qhov no qhia txog kev sib cuam tshuam sib txuas ntawm Kisspeptin neurons thiab lwm yam neuropeptides hauv kev tswj hwm neuroendocrine, sib sau ua ke tswj hwm pulsatile hormone secretion ^[2].

Daim duab 1 Histograms qhia qhov feem pua ​​​​ntawm cov kev sim uas tshwm sim los ntawm calcium uas tshwm sim ntawm ARN^{KISS} neurons nyob rau hauv lub hlwb hlais nyob rau hauv unstimulated tej yam kev mob thiab ua raws li tsawg zaus thiab ntau zaus stimulation ntawm ib tug neuron nyob rau hauv tsis muaj thiab muaj CNQX los yog neurokinin receptor (NKR) antagonists.  

Source: PubMed ^[3].

Dab tsi yog qhov kev nce qib ntawm kev tshawb fawb soj ntsuam ntawm Kisspeptin hauv kev kho cov kab mob metabolic?

Kisspeptin thiab Hom 2 Mob ntshav qab zib mellitus (T2DM)  

Kev tswj hwm ntawm Glucose Metabolism: Cov yam ntxwv tseem ceeb ntawm T2DM muaj xws li insulin tsis kam, tsis txaus insulin secretion, thiab nce ntshav qabzib. Cov kev tshawb fawb qhia tias Kisspeptin tuaj yeem tswj cov piam thaj metabolism hauv ntau txoj hauv kev. Ntawm ib sab tes, Kisspeptin tuaj yeem cuam tshuam rau insulin rhiab heev; Ntawm qhov tod tes, nws tuaj yeem ua rau pancreatic islet β-cell muaj nuj nqi kom cuam tshuam rau kev tso tawm insulin.  

Kisspeptin thiab Obesity  

Kev tswj hwm lub zog sib npaug thiab kev noj zaub mov: Kev rog feem ntau cuam tshuam nrog lub zog tsis txaus vim kev siv zog ntau dhau thiab txo kev siv hluav taws xob. Kisspeptin tswj lub zog tshuav nyiaj li cas thiab noj tus cwj pwm hauv lub hauv paus paj hlwb. Kev nthuav qhia Kisspeptin nce ntxiv tuaj yeem txo cov zaub mov noj hauv cov tsiaj, thaum txo qis kev qhia tuaj yeem ua rau nws nce ntxiv, qhia tias Kisspeptin ua haujlwm tseem ceeb ntawm kev noj qab haus huv hauv cov kab mob ntawm kev rog.  

Kisspeptin thiab Non-Alcoholic Fatty Liver Disease (NAFLD)  

Kev cuam tshuam rau Hepatic Metabolism: NAFLD yog kab mob siab txuas nrog rau cov tshuaj insulin tsis kam thiab cov kab mob metabolic, uas tshwm sim los ntawm cov rog rog ntau dhau. Kisspeptin koom nrog hauv kev tswj cov kab mob siab metabolic. Hauv kev sim tsiaj, kev cuam tshuam Kisspeptin tau pom tias yuav hloov pauv cov lipid metabolism, cov lus teb inflammatory, thiab oxidative kev nyuaj siab hauv daim siab. Nws tuaj yeem txo cov rog rog los ntawm kev tswj hwm cov haujlwm ntawm cov enzymes tseem ceeb koom nrog hauv fatty acid synthesis thiab tawg. Tsis tas li ntawd, Kisspeptin tuaj yeem hloov kho cov kab mob hepatic inflammatory signaling txoj hauv kev los txo qhov mob thiab qeeb NAFLD.  

Kisspeptin thiab Polycystic Ovary Syndrome (PCOS)  

Dual Regulation of Reproductive Endocrinology and Metabolism: PCOS yog ib hom kab mob endocrine thiab metabolic uas tshwm sim los ntawm ob qho tib si kev ua me nyuam endocrine txawv txav thiab cov piam thaj-lipid metabolic mob hauv cov neeg mob feem ntau. Kisspeptin plays lub luag haujlwm tseem ceeb hauv PCOS pathogenesis. Centrally, nws tswj cov hypothalamic-pituitary-gonadal axis los cuam tshuam kev ua me nyuam endocrinology hauv PCOS cov neeg mob. Lub caij no, nws koom nrog cov txheej txheem metabolic uas suav nrog insulin, leptin, thiab adiponectin, qhia tias nws yog qhov tseem ceeb hauv kev ua haujlwm metabolic hauv PCOS.  

Kev siv Kisspeptin yog dab tsi?  

Kev kho mob ntawm cov kab mob hauv cov menyuam yaus  

Kev loj hlob tsis zoo rau Pubertal: Kisspeptin yog qhov tseem ceeb rau kev pib puberty. Cov kev tshawb fawb qhia tau tias kev hloov pauv hauv Kisspeptin-GPR54 tuaj yeem ua rau ncua sijhawm puberty lossis hypogonadism. Exogenous kev tswj hwm ntawm Kisspeptin tuaj yeem txhawb nqa HPG axis los txhawb GnRH thiab gonadotropin secretion, tuav cov lus cog tseg rau kev kho cov kab mob pubertal. Piv txwv li, nyob rau hauv cov neeg mob uas muaj hypogonadism vim Kisspeptin signaling tsis xws luag, supplementation nrog Kisspeptin los yog nws cov analogs tuaj yeem rov ua dua qub kev loj hlob ^{[4, 5]}.  

Ovulation Disorders: Hauv cov poj niam cev xeeb tub, Kisspeptin tswj kev coj khaub ncaws thiab ovulation. Nws muaj peev xwm kho tau tus nqi rau cov kab mob ovulation xws li PCOS. Los ntawm kev tswj hwm GnRH pulsatile secretion, Kisspeptin tuaj yeem hloov kho gonadotropin tso tawm los txhim kho follicular kev loj hlob thiab ovulation. Cov kev tshawb fawb soj ntsuam pom tau hais tias Kisspeptin induces ib tug ntau physiological gonadotropin secretion qauv nyob rau hauv ib co ovulation disorder cov neeg mob, pab txhawb ovulation kev vam meej ^{[5, 6]}.  

Functional Hypothalamic Amenorrhea (FHA): FHA yog tshwm sim los ntawm qhov txawv txav GnRH pulsatile secretion hauv hypothalamus. Raws li tus tswj hwm ntawm GnRH, Kisspeptin yog qhov tseem ceeb rau kev kho FHA. Cov kev tshawb fawb qhia tau hais tias kev tswj hwm ntawm Kisspeptin-54 rau cov neeg mob FHA muaj txiaj ntsig zoo txhawb nqa gonadotropin (FSH, LH) tso tawm, tuav cov lus cog tseg rau kev rov ua kom muaj kev coj khaub ncaws thiab fertility. Qhov no muab cov tswv yim tshiab rau kev kho FHA ^[6].  

Kev kho mob ntawm cov kab mob metabolic  

Non-Alcoholic Fatty Liver Disease (NAFLD): Cov kev tshawb fawb tsis ntev los no tau pom tias ua rau Kisspeptin 1 receptor (KISS1R) qhia txoj hauv kev muaj kev kho mob ntawm NAFLD. Hauv cov qauv kev noj zaub mov uas muaj rog rog, cov kab mob siab Kiss1r ua rau mob siab steatosis, thaum txhim kho KISS1R stimulation tiv thaiv cov nas qus los ntawm steatosis thiab txo cov kab mob siab hauv cov khoom noj uas tsis muaj cawv steatohepatitis (NASH) nas. Cov kev tshawb fawb Mechanistic qhia tau hais tias lub siab KISS1R signaling txhim kho NAFLD kev nce qib los ntawm kev ua kom AMPK, lub zog tseem ceeb tswj cov qauv, kom txo lipogenesis. Tsis tas li ntawd, nce qib hepatic KISS1 / KISS1R thiab plasma Kisspeptin qib hauv cov neeg mob NAFLD thiab cov nas noj zaub mov muaj roj ntau qhia txog kev siv nyiaj los txo qis triglyceride synthesis, ua rau KISS1R yog lub hom phiaj tshiab rau kev kho NASH ^[7].  

Kev Kho Mob Osteoporosis: Osteoporosis yog ib hom kab mob metabolic pob txha uas cov tshuaj hormones kev loj hlob ua lub luag haujlwm tseem ceeb hauv kev loj hlob ntawm cov pob txha thiab kev tu vaj tse. Cov kev tshawb fawb pom tias Kisspeptin txhawb nqa kev sib txawv ntawm osteoblast thiab inhibits osteoclasts, muab kev kho mob rau kev kho pob txha. Cov txheej txheem yuav koom nrog kev tswj cov pob txha metabolic ntsig txog kev taw qhia txoj hauv kev, xws li Wnt txoj kev thiab RANKL-OPG system, los txhawb kev tsim cov pob txha, inhibit pob txha resorption, nce pob txha ceev, thiab txhim kho pob txha noj qab haus huv hauv cov neeg mob pob txha.  

Xaus

Txawm hais tias kev tshawb fawb soj ntsuam ntawm Kisspeptin hauv kev kho cov kab mob metabolic tau ua tiav, nws cov teebmeem cuam tshuam nrog ntau yam xws li cov piam thaj metabolism, lub zog sib npaug, cov metabolism hauv siab, thiab kev tswj hwm ntawm kev ua me nyuam endocrinology thiab cov metabolism.

Hais Txog Tus Sau

Cov ntaub ntawv hais saum toj no yog txhua yam tshawb fawb, kho thiab sau los ntawm Cocer Peptides.

Scientific Journal Author

Guzman, S yog tus kws tshaj lij hauv kev kho mob thiab kev tshawb fawb txog lub neej, koom nrog ntau lub tsev kawm muaj koob npe xws li Rutgers University System, Child Health Institute of New Jersey, thiab City University of New York (CUNY) System. Nws txoj kev tshawb fawb tsom mus rau Gastroenterology & Hepatology, Cell Biology, Reproductive Biology, thiab Obstetrics & Gynecology. Cov chaw tshawb fawb no tseem ceeb heev rau kev nce qib theoretical thiab kev kho mob ntawm cov tshuaj, qhia txog nws cov kws tshaj lij thiab kev cuam tshuam dav hauv kev tshawb fawb kho mob.. Guzman, S tau teev nyob rau hauv cov ntaub ntawv siv los ntawm citation [7].

▎ Cov Lus Qhia Tseem Ceeb

[1] Mills E, O'Byrne KT, Comninos A N. Kisspeptin as a Behavioral Hormone[J]. Seminars in Reproductive Medicine, 2019,37(2):56-63.DOI:10.1055/s-0039-3400239.

[2] Han SY, Morris PG, Kim JC, et al. Mechanism ntawm kisspeptin neuron synchronization rau pulsatile hormone secretion hauv txiv neej nas [J]. Cell Reports, 2023,42(1):111914.DOI:10.1016/j.celrep.2022.111914.

[3] Morris PG, Herbison A E. Mechanism ntawm Arcuate Kisspeptin Neuron Synchronization nyob rau hauv mob hlwb Slices Los ntawm poj niam nas[J]. Endocrinology, 2023,164(12).DOI:10.1210/endocr/bqad167.

[4] Sharma A. Scope ntawm Kisspeptin hauv Neuroendocrine Disorder [J]. 2023. DOI: 10.1093/humupd/dmu009.

[5] Tsoutsouki J, Abbara A, Dhillo W. Novel therapeutic avenues for kisspeptin[J]. Kev xav tam sim no hauv Pharmacology, 2022,67:102319.DOI:10.1016/j.coph.2022.102319.

[6] Podfigurna A, Czyzyk A, Szeliga A, et al. Kisspeptin Lub luag haujlwm hauv Kev Ua Haujlwm Hypothalamic Amenorrhea[M]//Berga SL, Genazzani AR, Naftolin F, thiab al. Menstrual Cycle Related Disorders: Volume 7: Frontiers in Gynecological Endocrinology. Cham: Springer International Publishing, 2019:27-42.DOI: 10.1007/978-3-030-14358-9_3.

[7] Guzman S, Dragan M, Kwon H, et al. Targeting hepatic kisspeptin receptor ameliorates nonalcoholic fatty siab kab mob hauv tus qauv nas [J]. Phau ntawv Journal of Clinical Investigation, 2022,132(10).DOI:10.1172/JCI145889.

Tag nrho cov kab lus thiab cov ntaub ntawv ntawm cov khoom lag luam muab rau ntawm lub vev xaib no tsuas yog rau cov ntaub ntawv tshaj tawm kev tshaj tawm thiab cov hom phiaj kev kawm.  

Cov khoom muab rau hauv lub vev xaib no yog npaj tshwj xeeb rau kev tshawb fawb hauv vitro. Kev tshawb fawb hauv vitro (Latin: * hauv iav *, lub ntsiab lus hauv iav) yog ua los ntawm tib neeg lub cev. Cov khoom no tsis yog tshuaj, tsis tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA), thiab yuav tsum tsis txhob siv los tiv thaiv, kho, lossis kho txhua yam mob, kab mob, lossis mob. Nws raug txwv nruj raws li txoj cai los qhia cov khoom no rau hauv tib neeg lossis tsiaj lub cev hauv txhua daim ntawv.