Protirelin Peptide

(I) Kev kuaj mob sib txawv ntawm Hypothyroidism Etiology

Qhov tseem ceeb ntawm kev kho mob daim ntawv thov ntawmprotirelin peptidenyob rau hauv qhov tseeb sib txawv ntawm thawj thiab theem nrab (pituitary / hypothalamic) hypothyroidism, hais txog cov kev txwv ntawm kev ntsuas cov ntshav T3, T4, thiab TSH. Thawj hypothyroidism tshwm sim los ntawm cov kab mob hauv cov thyroid caj pas, nrog cov qib TSH nce siab. Tom qab txhaj tshuaj ntawm protirelin (200-500 ug), pituitary TSH- zais cov hlwb pom cov lus teb zoo, nrog rau cov ntshav TSH siab tshaj plaws nce 3-5 npaug piv rau cov hauv paus, zoo ib yam nrog lub sijhawm ncov (15-30 feeb) pom hauv cov tib neeg noj qab haus huv.

Nyob rau hauv sib piv, theem nrab hypothyroidism tshwm sim los ntawm impaired anterior pituitary muaj nuj nqi; Txawm hais tias qis qis lossis qis qis li qub, TSH qhia tsis muaj qhov nce siab (peak < 2 × baseline) lossis qeeb teb tom qab txhaj tshuaj protirelin. Hypothalamic hypothyroidism tshwm sim raws li qhov qeeb TSH teb, nrog qhov siab tshaj plaws tshwm sim 60-90 feeb tom qab- txhaj tshuaj. Txoj kev no txheeb xyuas qhov chaw ntawm cov kab mob hypothyroid, muab cov pov thawj tseem ceeb rau kev tsim kho cov kev kho mob hloov kho, tshwj xeeb tshaj yog rau cov neeg mob occult hypothyroidism uas muaj ciam teb T3 / T4 qib thiab tsis muaj qhov txawv txav hauv basal TSH.

(II) Adjunctive Diagnosis of Graves' Disease thiab Endocrine Exophthalmos

Graves' kab mob (tshuaj lom diffuse goiter) yog ib qho autoimmune hyperthyroidism yam ntxwv los ntawm cov thyroid hormones ntau dhau (T3, T4), uas ua rau muaj kev cuam tshuam ntawm pituitary TSH - zais cov hlwb rau protirelin los ntawm kev tawm tswv yim tsis zoo. Hauv kev kuaj mob, cov neeg mob Graves' kab mob thiab cov kab mob endocrine exophthalmos qhia yuav luag tsis muaj kev nce ntxiv hauv cov ntshav TSH (ΔTSH < 2 mIU / L) tom qab txhaj tshuaj protirelin, thaum cov neeg noj qab haus huv pom muaj 2-3 npaug TSH siab txheeb ze rau hauv paus.

Qhov kev sim no pab kuaj mob atypical hyperthyroidism (piv txwv li, T3- toxicosis, subclinical hyperthyroidism) thiab ntsuas kev rov qab los ntawm pituitary-thyroid axis tom qab kho hyperthyroidism (cov tshuaj tiv thaiv kab mob, xov tooj cua iodine), txiav txim siab seb puas muaj cov thyroid hormone tsub kom txaus.

(III) Kev soj ntsuam ntawm Anterior Pituitary Reserve thiab Hypothalamic-Pituitary-Thyroid Axis Function

Kev ntsuam xyuas protirelin yog ib txoj hauv kev los ntsuas qhov kev ua haujlwm ntawm pituitary TSH secretion, tsim nyog rau kev tshuaj ntsuam endocrine hauv cov neeg mob uas xav tias hypopituitarism, qog nqaij hlav (xws li, pituitary adenomas), craniocerebral trauma, lossis post- radiotherapy. Los ntawm kev saib xyuas cov ntshav TSH qib ntawm ntau lub sijhawm cov ntsiab lus (0, 15, 30, 60, 90 feeb) tom qab- kev txhaj tshuaj, qhov kev ua haujlwm ntawm pituitary TSH hlwb tuaj yeem txiav txim siab: cov lus teb ib txwm qhia tias muaj peev xwm pituitary cia; ib qho blunted los yog tsis tuaj teb lus qhia impaired pituitary secretory muaj nuj nqi; thiab ncua sij hawm teb implies hypothalamic lesions.

Tsis tas li ntawd, qhov kev sim no tuaj yeem ua ke nrog gonadorelin (gonadotropin- tso cov tshuaj hormones) thiab kev loj hlob hormone stimulation tests los ntsuas ntau yam -hormonal secretion ntawm lub anterior pituitary thiab qhia meej txog qhov ntawm cov kab mob pituitary.Protirelin peptideKuj tseem pab tshawb xyuas qhov txaus ntawm cov thyroid hormone hloov kho ntau npaum li cas: hauv thawj cov neeg mob hypothyroid tau txais levothyroxine, ib txwm los yog me ntsis blunted TSH teb rau protirelin qhia txog kev hloov pauv ntau npaum li cas, thaum cov lus teb exaggerated qhia tias noj tsis txaus.

(I) Neurotransmitter Modulation thiab Central Nervous System Regulation

Protirelin ua tsis tau tsuas yog raws li ib tug endocrine hormone tab sis kuj yog ib qho tseem ceeb hauv nruab nrab neuromodulatory peptide. Nws cov receptors (TRH-R1, TRH-R2) tau dav dav hauv cerebral cortex, hippocampus, striatum, hypothalamus, thiab lwm thaj chaw, tswj kev tso tawm ntau yam neurotransmitters suav nrog dopamine, acetylcholine, 5-hydroxyluptamine, thiab glycemia.

Cov kev tshawb fawb paub meej tias protirelin txhawb nqa dopamine tso tawm hauv striatum thiab nucleus accumbens, modulating lub cev muaj zog ua haujlwm thiab nqi zog txoj hauv kev; txhawb nqa acetylcholine tso tawm hauv cortex thiab hippocampus, txhim kho kev paub thiab nco; thiab inhibits pathological ntau dhau glutamate tso tawm hauv hippocampus, txo excitatory neurotoxicity. Qhov dav dav neurotransmitter kev tswj hwm profile tsim protirelin ua ib qho tseem ceeb molecular cuab yeej hauv kev tshawb fawb neuropsychiatric teeb meem.

(II) Kev Tshawb Fawb Txog Kev Tshawb Fawb Txog Kev Nyuaj Siab

Cov kev tshawb fawb soj ntsuam thaum ntxov tau txheeb xyuas cov tshuaj tiv thaiv kev ntxhov siab sai ntawm protirelin, tshwj xeeb tshaj yog hauv kev kho mob -cov neeg mob kev nyuaj siab tiv taus tsis teb rau cov tshuaj tiv thaiv kev ntxhov siab. Tsis zoo li cov tshuaj ib txwm siv (uas siv sijhawm 2-4 lub lis piam los siv), cov tshuaj tua kab mob protirelin txhim kho cov tsos mob ntawm kev nyuaj siab xws li kev xav tsis zoo, anhedonia, thiab pw tsaug zog tsis zoo nyob rau ib teev.

Nws cov txheej txheem tuaj yeem cuam tshuam nrog kev hloov pauv sai ntawm central monoamine neurotransmitters (dopamine, 5-hydroxytryptamine) thiab thim rov qab HPT axis tsis ua haujlwm cuam tshuam nrog kev nyuaj siab (xws li, blunted TSH teb hauv qee cov neeg mob). Txawm li cas los xij, vim nws luv luv ib nrab- lub neej (tsuas yog feeb), qhov yuav tsum tau ua rau kev txhaj tshuaj hauv cov hlab ntsha, thiab cov kev mob tshwm sim tsis ntev los no suav nrog cov ntshav siab hloov pauv thiab xeev siab hauv qee tus neeg mob, protirelin tsis tau pom zoo ua tshuaj tiv thaiv kev nyuaj siab. Txawm li cas los xij, nws tau muab lub hauv paus tseem ceeb rau kev txhim kho ntawm TRH analogs ntev (xws li taltirelin).

(III) Neuroprotection thiab Neurodegenerative Disease Research

Neuroprotection los ntawm protirelin tau tshwm sim los ua ib qho kev tshawb fawb tseem ceeb hauv xyoo tas los no, kev kho mob feem ntau los ntawm peb lub tswv yim:

Inhibiting ntau glutamate tso tawm los thaiv excitotoxic neuronal apoptosis, tiv thaiv neural raug mob los ntawm cerebral ischemia, hypoxia, thiab xwm txheej epilepticus;

Txo oxidative kev nyuaj siab nyob rau hauv lub hlwb cov ntaub so ntswg, txo reactive oxygen hom-induced neuronal puas, thiab txhim kho neuronal anti-apoptotic muaj peev xwm;

Modulating neuroinflammation los ntawm suppressing ntau dhau microglial activation thiab txo pro-inflammatory cytokine tso (xws li, TNF- , IL-6).

Raws li, protirelin yog dav siv nyob rau hauv kev tshawb fawb preclinical ntawm Alzheimer's kab mob, Parkinson tus kab mob, amyotrophic lateral sclerosis (ALS), spinal cord raug mob, thiab lwm yam kab mob. Tsiaj thwmsim qhia tau hais tias protirelin alleviates kev kawm thiab nco impairments thiab txo -amyloid deposition nyob rau hauv Alzheimer tus kab mob nas qauv; relieves bradykinesia thiab tiv thaiv dopaminergic neurons hauv Parkinson tus kab mob qauv; thiab txhawb nqa kev ua haujlwm ntawm lub paj hlwb rov qab los tom qab kev raug mob ntawm tus txha caj qaum, txhim kho lub cev nqaij daim tawv thiab kev hnov ​​​​mob. Tsis tas li ntawd,protirelin peptideua hauj lwm pab raws li kev kho mob rau cov teeb meem ntawm kev nco qab (piv txwv li, post- mob coma), pab txhawb kev nco qab los ntawm kev ua kom lub hauv nruab nrab neural pathways.

(I) Mechanistic Research ntawm Hypothalamic-Pituitary-Thyroid (HPT) Axis

Protirelin ua hauj lwm raws li tustxheem peptide cuab yeejrau kev tshawb fawb HPT axis yooj yim, feem ntau siv rau hauv vitro cellular assays thiab tsiaj qauv. Hauv vitro, protirelin stimulation ntawm anterior pituitary hlwb ua rau kev tshawb nrhiav TSH thiab PRL synthesis thiab secretion regulatory mechanisms, characterization of TRH receptor signaling pathways (G protein coupling, cAMP, Ca²⁺ influx), thiab tshuaj ntsuam HPT axis -modulating tshuaj.

Hauv vivo, siv cov qauv hypothyroid, hyperthyroid, thiab hypophysectomized tsiaj qauv, kev ntsuas cov ntshav TSH, T3, thiab T4 hloov tom qab-protirelin txhaj qhia meej txog HPT axis tawm tswv yim kev cai, kev ua haujlwm loj thaum loj hlob, thiab cuam tshuam ntawm ib puag ncig (xws li, kev ntxhov siab, khoom noj khoom haus) ntawm cov kab mob endocrine. Protirelin kuj tseem pab txhawb kev tshawb fawb ntawm TRH tus ntoo khaub lig- tswj lub luag haujlwm hauv cov tsis yog -thyroid endocrine axes, suav nrog hypothalamic-pituitary-adrenal axis thiab loj hlob hormone axis.

(II) Prolactin (PRL) Txoj Cai Tiv Thaiv Kev Tiv Thaiv thiab Kev Tshawb Fawb Txog Kab Mob

Protirelin tshwj xeeb txhawb nqa pituitary lactotrophs kom zais PRL, ua rau nws yog ib qho tseem ceeb rau kev kawm hyperprolactinemia thiab pituitary prolactinomas.

Hauv kev tshawb fawb preclinical, protirelin stimulation test ntsuas lactotroph responsiveness, paub qhov txawv ntawm kev ua haujlwm hyperprolactinemia los ntawm prolactinomas (tus cwj pwm los ntawm qhov nce siab basal PRL thiab blunted teb rau protirelin). Tib lub sijhawm, protirelin yog siv los tshawb xyuas PRL lub luag haujlwm hauv kev loj hlob ntawm mammary, kev ua haujlwm ntawm kev ua me nyuam, thiab kev tiv thaiv kab mob, nrog rau cov txheej txheem ntawm TRH-PRL txoj hauv kev hauv polycystic zes qe menyuam syndrome, kev nyuaj siab tom qab yug me nyuam, thiab lwm yam kab mob.