Gonadotropin-tso lawm (GnRH): tshwj xeeb tshaj yog cov tshuaj thiab analogs

Gonadotropin-tso lawm (GnRH) yog hu ua ib tug lawm uas tawm luteinizing hormone (LHRH) thiab lyuliberin uas yog ib tug peptide trophic lawm lub luag hauj lwm rau qhov kev tso tawm ntawm FSH (follicle stimulating hormone), thiab (LH), luteinizing hormone los ntawm lub anterior pituitary. GnRH - ib yam tshuaj tsim thiab tso tawm nyob rau hauv lub hypothalamus ntawm GnRH neurons. Qhov no peptide belongs rau ib tsev neeg ntawm gonadotropin-tso lawm thiab cov sawv cev osinachalny kauj ruam hypothalamic-pituitary-adrenal system. Qhov no daim ntawv yuav tsum tau nthuav tawm raws li antagonists ntawm gonadotropin-tso lawm.

qauv

Nobel laureates, Andrew V. Schally thiab Rozhe Giymen piav nyob rau hauv 1977 qhia yam ntxwv GnRH: piroGlyu-Giese-Trp-Ser-Tyr-Gly-Leu-arg-Pro-Gly-NH2. Yuav ua li cas yog ib qho nyob rau hauv qhov kev nthuav qhia ntawm peptides, ib theem zuj zus muab los ntawm N-terminus rau C-terminus rau peptide kev nthuav qhia, raws li ib txwm, tab sis kuj yog ib tug txheej txheem hla chirality los, tawm tswv yim tias cov amino acids nyob rau hauv lub L-zoo nyob. Qhov saum toj no abbreviations yog standard proteinogenic amino acids. Tsuas yog ib tug yog piroGlyu - pyroglutamic acid, ib tug derivative ntawm glutamic acid. Thaum lub C-terminus NH2 ntawd hais tias cov saw xaus karboksidaminom es tsis txhob ntawm free carboxylate.

synthesis

Cov precursor ntawm gonadotropin-tso lawm noob GNRH1 nyob rau hauv chromosome 8 8. qub mammalian decapeptide tsim 92 amino acid pre-prohormone nyob rau hauv pem hauv ntej preoptic hypothalamus. Nws yog ib lub hom phiaj rau txawv system mechanisms regulating hypothalamic-pituitary-adrenal axis inhibited los ntawm kev ua theem ntawm cov tshuaj no nyob rau hauv lub cev.

functionality

Gonadotropin-tso lawm yog secreted mus rau hauv cov ntshav ndlwg ntawm lub portal cov hlab ntsha pituitary cheeb tsam ntawm lub median eminence. GnRH yog pauv mus rau lub pituitary ntshav ndlwg ntawm lub portal cov hlab ntsha uas muaj gonadotropic hlwb nyob qhov twg tus kheej receptors activates GnRH receptor lawm gonadotropin-tso, xya transmembrane receptors uas conjugated nrog lub G-protein thiab stimulating lub beta isoform phosphoinositide phospholipase C, uas kis tau mus rau lub mobilization ntawm protein kinase C thiab calcium . Qhov no los tau nyob rau hauv qhov ua kom ntawm cov nqaijrog uas muab kev koom tes nyob rau hauv lub tso pa tawm thiab synthesis ntawm cov gonadotropins FSH thiab LH. Thaum lub sij hawm proteolysis GnRH phua rau ob peb feeb. Raws li ib tug me nyuam, txoj kev yog heev tsawg, ua nyob rau hauv thaum tiav hluas los yog tiav hluas. Tau zoo nyob rau hauv lub tsev me nyuam muaj nuj nqi pulsatility kev ua si yog critically tshuaj los ntawm ib tug tswv yim voj. Tab sis GnRH ua si thaum lub sij hawm cev xeeb tub tsis yuav tsum tau. Kab Mob los yog tsis ua hauj lwm, raws li zoo raws li organic kev puas tsuaj thiab raug mob yam hypothalamus thiab pituitary hlav tej zaum yuav ua undesired pulsatility kev ua si. Tsa prolactin theem txo cov kev ua ntawm GnRH, hyperinsulinemia thiab nws nce thiab ua rau ib tug disturbance ntawm cov kev ua ntawm FSH thiab LH, xws li nyob rau hauv polycystic zes qe menyuam. Kallmana syndrome yog tsiag ntawv los ntawm kev qhaj ntawv ntawm GnRH synthesis.

neurohormones

GnRH yuav ntaus nqi rau lub neurohormones. Ua gonadotropin-tso lawm nyob rau hauv lub preoptic cheeb tsam muaj feem ntau ntawm cov GnRH-secreting neurons. Cov neurons xeeb nyob rau hauv lub qhov ntswg ntaub so ntswg thiab migrate mus rau lub hlwb nyob qhov twg nyob rau hauv lub nrub nrab septum thiab ces dispersed nyob rau hauv lub hypothalamus kev cob cog rua nrog ntev dendrites, ntau tshaj 1 hli ntev. Lub synchronization GnRH tso lawv mus rau hauv bundles compound yuav pab tau tsim muaj ib zaug xwb synaptic inputs. Siv ib tug xov tooj ntawm txawv transmitters xws li GABA, glutamate thiab norepinephrine tswj GnRH secreting neurons. Narpimer, tom qab thawj coj ntawm progesterone-tshuaj poj niam dopamine nkoos qhov kev tso tawm ntawm LH; thiab ovariectomized cov poj niam dopamine yuav inhibit qhov kev tso tawm ntawm LH. Qhov tseem ceeb tshaj regulator ntawm kev tso tawm ntawm GnRH hnia-peptin tej zaum kuj yuav yog tswj los ntawm cov tshuaj no. Txawm li cas los, muaj ib lub hav zoov ntawm neuronal secreting hnia-peptin thiab hnov txog cov alpha thiab cov tshuaj no receptors.

Nws yog ib qho tseem ceeb kom paub tias dab tsi yog agonists ntawm gonadotropin-tso lawm. Qhov tsab xov xwm yuav tsum tau cov ntaub ntawv hais txog nws.

Impact on lwm yam kabmob

Lub luag hauj lwm ntawm GnRH tsis zoo kawm nyob rau hauv cov txheej txheem ntawm lub neej nyob rau hauv tas li ntawd mus rau lub pituitary caj pas thiab lub hypothalamus. Muaj ib tug tau hais tias nws muaj ib cov nyhuv rau tus txiv neej pw qog thiab lub tsho me nyuam kuj GnRH receptors thiab GnRH nws tus kheej tau pom nyob rau hauv cov kev mob hlwb, ntawm zes qe menyuam, endometrial, prostate, thiab ob lub mis.

Los rau tus cwj pwm

Cov cwj pwm ntawm zus tau tej cov tshuaj GnRH yog tseem cuam tshuam. Cov tsev neeg ntawm cichlid fishes ntses uas qhia kev dominance, muaj enhanced kev cai ntawm GnRH secretion, thaum kev rhiab cichlids muaj ib tug txo kev cai ntawm GnRH secretion. Qhov luaj li cas ntawm cov neurons uas paim GnRH nyob rau tus cwj pwm thiab cov kev sib raug ib puag ncig. Ntau caug muaj cais loj loj secreting GnRH neurons ches caug tsawg cais. Ua taus zes maum kuj muaj ib tug me me npaum li cas ntawm neurons tshaj nyob rau hauv lub pab pawg neeg tswj cov maum. Nws hais txog kev cai ntawm GnRH lawm.

Agonists ntawm gonadotropin-tso lawm yuav sib tham txog hauv qab no.

Kev kho mob daim ntawv sau npe

Rau cov kev kho mob ntawm cov neeg mob ua ntej muab tej yam ntuj tso GnRH li gonadorelin hydrochloride (Faktrel) thiab diatsetattetragidrata gonadorelin (Tsistorelin). Kev hloov kho GnRH dekapiptida qauv tau coj mus rau lub creation ntawm tshwj xeeb, stimulating los yog suppressing gonadotropins cas sim haum ib nrab-lub neej. Thiab cov hluavtaws analogs ntawm lub ntuj lawm twb hloov. Leuprorelin analog siv rau kev kho mob ntawm endometriosis, mis kartsiomy, prostate kartsiomy thiab tom qab ib txhia xyoo ntawm kev tshawb fawb nyob rau hauv 1980, nyob rau hauv Vol. H. Komita ua los ntawm Dr. Florence los ntawm Yale University, rau kev kho mob ntawm precocious tiav nkauj tiav nraug, raws li ib tug tas mus li Txoj kev lis ntshav.

Gonadotropin-tso lawm: tus nqi

Qhov nruab nrab nqi ntawm ib tug raj mis - los ntawm 300 rubles.

Tsiaj Kev sib deev cwj pwm

Txawv kuj tshwm sim los ntawm kev sib deev tus cwj pwm kev ua ntawm GnRH. Piv txwv li, kho kom zoo ua qauv qhia poj niam deev tus cwj pwm ua rau ib qho kev nce rau hauv cov theem ntawm GnRH. Nyob rau hauv dawb-crowned sparrow nce coob copulation tom qab cov kev taw qhia ntawm GnRH, thiab kho kom zoo nyob rau hauv cov tsiaj ua qauv qhia kev sib deev tus cwj pwm nyob rau hauv cov maum, uas yuav tsum tau pom nyob rau hauv ntev-tailed dawb-toothed shrew thiab nws latent lub sij hawm poob thaum lub sij hawm ua tus qauv qhia rau sab nraum qab ntawm tus txiv neej thiab lub zog nyob rau hauv nws cov kev taw qhia ntawm tus Tsov tus tw. Nws tej cov kev ua ntawm testosterone caug nce los ntawm GnRH saum toj no ib txwm theem ntawm testosterone kev ua si. Deterioration GnRH ua hauj lwm ua ib tug aversive nyhuv physiology ntawm tu tub tu kiv thiab niam tus cwj pwm. Yog hais tias peb los sib piv cov poj niam nas thaum lub sij hawm ib txwm system ntawm GnRH, cov maum ntau muaj kev txhawj xeeb txog xeeb leej xeeb ntxwv tshaj nrog ib tug txo tus naj npawb ntawm neurons los ntawm 30%. Feem ntau cov yuav, cov nas yuav tawm pups nyias, uas ua nyob rau hauv ib tug ntev nrhiav tau lawv.

Veterinary daim ntaub ntawv

Qhov uas siv tau gonadotropin-tso lawm? Tshuaj siv nyob rau hauv kev kho tsiaj raws li ib tug tshuaj rau cov kev kho mob ntawm cystic ntawm zes qe menyuam kab mob nyob rau hauv nyuj. Ib tug hluavtaws analogue thereof, deslorelin siv rau kho tsiaj tswj ntawm kev ua me nyuam functions siv cov cog thiab lub pab tso tawm formulation.

Xav txog analogues ntawm gonadotropin-tso lawm.

Agonists thiab antagonists ntawm gonadotropin-tso lawm

Nyias, ib pab pawg neeg ntawm cov tshuaj uas feem mechanism yuav rightly yuav hu ua ib tug agonist ntawm gonadotropin-tso lawm. Qhov no txhais tau tias cov nyhuv ntawm no pab pawg neeg ntawm cov tshuaj nyob rau hauv lub caj pas pituitary ua ib cov nyhuv tib yam rau cov nyhuv ntawm nws tus kheej lawm. Cov neeg sawv cev ntawm no pab pawg neeg yuav hu ua "Sinarel", "Lyukrin Gonapeptil depot." Qhov no agonist ntawm gonadotropin-tso lawm. Lub formulations yog siv ua ntej thiab tom qab kev kho mob ntawm fibroids, endometriosis thiab ua ntej surgically tshem lub tsev me nyuam (hysterectomy) nyob rau hauv cov kev kho mob ntxiv lawm tshob. Active tshuaj nyob rau hauv tus ntawm pais plab kua txiv so thiab yog li ntawd tag nrho cov tshuaj yog txhaj cov nyob hauv daim tawv nqaij los yog rau hauv cov nqaij interanazolno.

Los ntawm gonadotropin-tso lawm antagonists yog "Tsetrotid" ( "Tsetroteriks"), "ganirelix" thiab li ntawd.