Gonadotropin-kusunungura kemikari (GnRH): kunyanya zvinodhaka uye analogs

Gonadotropin-kusunungura kemikari (GnRH) inozivikanwa se hormone iyo anosunungura luteinizing kemikari (LHRH) uye lyuliberin inova peptide trophic kemikari anokonzera kusunungurwa FSH (follicle anotokonya kemikari), uye (LH), luteinizing kemikari kubva Anterior pituitary. GnRH - hormone synthesized uye kusunungurwa hypothalamus pamusoro GnRH Tutsinga tunofambisa mashoko utwu. peptide ichi yedzinza mhuri gonadotropin-kusunungurwa kemikari uye anomiririra osinachalny danho hypothalamic-pituitary-adrenal hurongwa. bepa Izvi zvichakurukurwa sezvo mhandu kubva gonadotropin-kusunungura kemikari.

mamiriro

Nobel laureates, Andrew V. Schally uye Rozhe Giymen akatsanangura muna 1977 kuziva unhu GnRH: piroGlyu-Giese-TRP-water-Tyr-Gly-Leu-Arg-Pro-Gly-NH2. Kweinozivikanwa iri mharidzo peptides, kutevedzana akapiwa N-Terminus kuti C-Terminus nokuda peptide mharidzo, senguva dzose, asiwo mureza yokupembera chirality rokuti, zvichireva kuti amino acids vari L-chimiro dziri. The pamusoro abbreviations vane mwero proteinogenic amino acids. An Kunze ndiko piroGlyu - pyroglutamic acid, rinobva pane glutamic acid. Panguva C-Terminus NH2 kunoratidza kuti cheni unoguma karboksidaminom pane akasununguka carboxylate.

kwetunhu

The aizotangira pamusoro gonadotropin-kusunungura kemikari Gene GNRH1 yaiva chromosome 8 8. Normal mammalian decapeptide synthesized 92 amino asidhi kwerubwinyo rwakagara rwuripo prohormone pamberi preoptic hypothalamus. Zviri atambudzwe zvakasiyana hurongwa zvigadziriswe yokudzora hypothalamic-pituitary-adrenal akabatana hwakaipa nokuwedzera kwevari inonzi estrogen pamuviri.

functionality

Gonadotropin-kusunungura kemikari iri secreted kupinda ropa unyatsoshanda portal tsinga pituitary munharaunda evaMedhia yapamusoro. GnRH ari hwakatamisirwa pituitary shwanu ropa unyatsoshanda portal tsinga ine masero gonadotropic, apo receptors dzavo zvaanopa simba GnRH receptors kemikari inonzi gonadotropin-kwokusunungura 7 Kanotokonya transmembrane kuti nechokuita G-mapuroteni uye vabatsire Beta-isoform kuti phosphoinositide phospholipase C, iyo inopfuura kuti kuunganidza mapuroteni kinase C uye calcium yakawanda . Izvi inoguma activation kwemapurotini kuti vanobatanidzwa munyaya secretion uye kwetunhu gonadotropins FSH uye LH. Panguva proteolysis GnRH akatsemura kwemaminitsi mashoma. Somwana, kwayakaita yakaderera chaizvo, achiwedzera kuyaruka kana kuyaruka. Kubudirira kunobva okubereka basa pulsatility kuita achitsoropodza zvinodzorwa nerimwe dzinovaka loop. Asi GnRH mumwaka pamuviri havadikanwi. Zvirwere kana dysfunction, uyewo makemikari zvakakanganisika uye kukuvara mhando hypothalamus uye pituitary mapundu zvingakonzera undesired pulsatility basa. Kwakakwidziridzwa prolactin yomuropa zvinoderedza nezvebasa GnRH, hyperinsulinemia uye unomutswa uye chinoita nyonganyonga webasa FSH uye LH, dzakadai polycystic ovaries. Kallmana chirwere kunoratidzwa asipo GnRH kwetunhu.

neurohormones

GnRH anogona kunzi kune neurohormones. Yakabudiswa gonadotropin-ichibudisa kemikari munzvimbo preoptic nharaunda kuitika zvakawanda GnRH-secreting Tutsinga tunofambisa mashoko utwu. Tutsinga tunofambisa mashoko utwu izvi kunobuda nasal nyama uye tama kuuropi apo ari medial septum uye vakapararira hypothalamus kwakabatana dendrites refu, anopfuura 1 mm refu. Yaunonyanya kushandisa GnRH kusunungura navo mwanda remubatanidzwa kunobatsira kuti pave chete synaptic zvinoshandisa pakurima. Kushandisa nhamba dzakasiyana zvinotakura akadai neGhebha, glutamate uye norepinephrine yaidzorwa GnRH secreting Tutsinga tunofambisa mashoko utwu. Narpimer, pashure kwokubatsira progesterone-inonzi estrogen vakadzi dopamine kunomutsa kusunungurwa LH; uye ovariectomized vakadzi dopamine anogona tunodzivisa nokubudiswa LH. Anokosha regulator kuti vasunungurwe GnRH Kiss-peptin zvinogona nokudzorwa inonzi estrogen. Zvisinei, paiva ariko neuronal secreting Kiss-peptin uye kutaura Arufa inonzi estrogen receptors.

Zvakakosha kuziva kuti muri agonists kuti gonadotropin-kusunungura kemikari. Nyaya ino chichava ruzivo nezvazvo.

Impact pane dzimwe nhengo

Basa GnRH havaratidzi akadzidza ari dzinotsanagura upenyu kuwedzera pituitary shwanu uye hypothalamus. Pane mukana kuti ane zvainoita bonde omumuviri uye placenta uyewo GnRH receptors uye GnRH pacharo akawanikwa mumasero kenza, ovarian, endometrial, prostate, uye zamu.

Zvinoitika maitiro

Unhu pagadzirwe kemikari GnRH ari kukanganiswa. Mhuri cichlid nehove hove kuratidza evanhu kutonga, vachiona kunowedzera mutemo GnRH secretion, kana tichinetseka mumagariro cichlids vane kwakaderedza mutemo GnRH secretion. Ukuru Tutsinga tunofambisa mashoko utwu kuti secrete GnRH novimba maitiro uye munzanga kwezvakatipoteredza. vanhurume More nevachena guru saizi secreting GnRH Tutsinga tunofambisa mashoko utwu ches vechirume zvishoma yoga. Rutoto vakadzi vane shoma Tutsinga tunofambisa mashoko utwu kupfuura kudzorwa boka vanhukadzi. It anotaura evanhu mutemo GnRH kemikari.

Agonists kuti gonadotropin-kusunungura kemikari zvinokurukurwa pazasi.

Medical mafomu

Nokuti kurapa vanhu vanorwara vasati ushandiswe dzinongoitika GnRH sezvo gonadorelin hydrochloride (Faktrel) uye diatsetattetragidrata gonadorelin (Tsistorelin). Nadzurudzo GnRH dekapiptida mamiriro zvakakonzera kusikwa nemamwe, anotokonya kana kudzvanyirira gonadotropins kurebesa hafu-upenyu. Uye izvi chakaita zvokugadzirwa analogs zvakasikwa kemikari akatsiviwa. Leuprorelin analoginen rakashandiswa Mabatirwo endometriosis, zamu kartsiomy, prostate kartsiomy uyewo pashure makore tsvakurudzo muna 1980, muna Vol. H. Komita kwaitungamirirwa Dr. Florence kubva Yale University, nokuti Mabatirwo precocious kuyaruka, sezvo chinoramba aizomupa.

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Animal Zvepabonde

Kusiyana vanoitwa kunokonzerwa dzepabonde basa GnRH. Somuenzaniso, kunowedzera Kuratidzwa hadzi dzepabonde kunokonzera kuwedzera huwandu GnRH. In chena-korona shiri kwakawedzera kudiwa yomurume pashure okusuma GnRH, uye chakaiswa panzvimbo mhuka mukuratidza dzepabonde mune vakadzi, iyo inogona kuchengetwa pamusoro refu-tailed chena-toothed shrew chacho Isimba rakadini rinogona kubudiswa nguva kuderera panguva kuratidzwa shure mukono sangano iri kutungamirirwa yake muswe. It runogonesa rinoitwa testosterone varume yakawedzera GnRH kupfuura dzose pamwero testosterone basa. Kudzikira GnRH basa kunokonzera ane aversive mugumisiro physiology wokuberekana uye rwaamai maitiro. Kana tikaenzanisa hadzi makonzo munguva chakaipa hurongwa GnRH, nhunzvi vanonyanya kunetseka zvizvarwa pane imwe kwakaderedza nhamba Tutsinga tunofambisa mashoko utwu kubudikidza 30%. Ungangove, mbeva izvi achasiya pups vachiravana, zvichiguma rebei kudziwana.

Veterinary mafomu

Apo zvinoshanda gonadotropin-kusunungura kemikari? Drugs akashandiswa wemhuka sezvo mushonga pakurapa cystic ovarian chirwere mune mombe. A chakaita zvokugadzirwa analogue kwayo, deslorelin yaishandiswa wemhuka kudzora dzokubereka mashandiro vachishandisa kudyara uye kuramba kusunungurwa Pfungwa.

Funga analogues kuti gonadotropin-kusunungura kemikari.

Agonists uye mhandu ose gonadotropin-kusunungura kemikari

Oga, boka zvinodhaka izvo aaiitawo mashandiro anogona kunzi ane agonist kuti gonadotropin-kusunungura kemikari. Izvi zvinoreva kuti nezvaizoitwa boka iri zvinodhaka pamusoro pituitary shwanu kunokonzera chimwe chinhu akafanana kuti mugumisiro wayo kemikari. Vamiririri boka iri vanogona kunzi "Sinarel", "Lyukrin Gonapeptil dhepoti." agonist ichi gonadotropin-kusunungura kemikari. The Formulations anechekuita vasati uye pashure vabatwe fibroids, endometriosis uye napamberi surgically dzichibvisa dumbu (chibereko) pakurapa mbereko. Active zvinhu pasi pokudzora gastric muto yemasikati uye saka zvinodhaka vose jekiseni pasi ganda kana kupinda tsandanyama interanazolno.

Pakazosvika gonadotropin-kusunungura kemikari mhandu vari "Tsetrotid" ( "Tsetroteriks"), "ganirelix" uye nezvakadaro.