Ho imeloa kelellong le botenya: Pono e ncha ea "lijo tsa matšeliso" (2003)

. 2003 Sep 30; 100 (20): 11696-11701.

E hatisitsoe Inthaneteng 2003 Sep 15. doi:  10.1073 / pnas.1934666100

PMCID: PMC208820

Khopolo-taba

inahaneloang

Litla-morao tsa adrenal corticosteroids ka sekhukhu se sireletsang adrenocorticotropin li rarahane. Ha e le hantle (ka mor'a lihora tse seng kae), glucocorticoids (GCs) e thibela ka ho toba mosebetsi o mong oa hypothalamo-pituitary-adrenal axis, empa liketso tse sa foleng (matsatsing a mangata) a steroid tsena likoetleng li itšetlehile ka ho toba. Maemo a mangata a nako e telele a GC a sebetsa ka litsela tse tharo tse sebetsang hantle. (i) Li-GC li eketsa polelo ea mRNA ea corticotropin-releasing factor (CRF) karolong e ka hare ea amygdala, e leng node e boima ka boko ba maikutlo. CRF e nolofalletsa batho hore ba fumane kopano e sa feleng ea khatello ea maikutlo. (ii) Li-GC li eketsa bokhoni ba mesebetsi e thabisang kapa e qobelloang (ho noa sucrose, mafura le lithethefatsi, kapa likoloi). Sena se susumelletsa ho kenngoa ha "lijo tsa matšeliso." (iii) Li-GC li sebetsa ka mokhoa oa ho eketsa li-depot tsa mafura a mpa. Sena se lumella pontšo e eketsehileng ea mabenkele a matla a mpa ho thibela catecholamines ka boitsebiso ba kelello le CRF ho li-neurons tsa hypothalamic tse laolang adrenocorticotropin. Ho imeloa kelellong, hammoho le likhahla tse phahameng tsa GC, hangata ho fokotsa boima ba 'mele ka likhoto; ka lehlakoreng le leng, batho ba imetsoeng kapa ba tepeletseng maikutlo ba imetsoeng ke khatello ea kelello ho eketsa lijo tse matlafatsang lijo le boima ba 'mele kapa ho fokotsa boima ba' mele le ho fokotsa 'mele. Ho tšelisoa ke lijo tse hlahisang botenya bo ka mpeng, ho fokotsa moriana oa CRF ho ea hypothalamus ea likhoto. Batho ba tepelletseng maikutlong ba jang lijo tse ngata haholo ba fokotsehile cerebrospinal CRF, lihlopha tsa catecholamine le hypothalamo-pituitary-adrenal activity. Re etsa tlhahiso ea hore batho ba ja lijo tsa matšeliso ka boiteko ba ho fokotsa mosebetsi ka ho sa feleng oa likarabo tsa khatello ea maikutlo le ho tšoenyeha ha mohlanka. Mekhoa ena, e khethiloeng ka likhoto, e ka hlalosa tse ling tsa seoa sa botenya bo hlahelang sechabeng sa rona.

Keywords: motsoako oa corticotropin-release, glucocorticoids, mafura a phahameng, sucrose, tšusumetso

Tlhaloso ea rona ea tsamaiso ea ts'ebetso ea hypothalamo-pituitary-adrenal (HPA) axis e fetohile haholo lilemong tse mashome a fetileng. Ho fumanoa ha mesebetsi ea lihlopha tse arolelitsoeng tsa neurons tsa corticotropin-release (CRF), li-neurons tsa motlakase bakeng sa ts'ebetso ea pituitary le li-adrenal, hammoho le likamano tse matla pakeng tsa lik'hilojule, boima ba 'mele, lisebelisoa tsa matla le li-axis tsa HPA re kile ra ba le liphetoho mehopolong ea rona. The upshot ke mohlala o mocha o sebetsang, o hlahisoang ke oona o fetoletsoeng ka ho sebelisa mokhoa oa caloric input (Feie. 1). Liphello tsa nako e telele tsa liphetoho tse joalo tse fetotsoeng ho batho ba nang le khatello ea kelello e ka 'na ea kenyelletsa leruo la boima bo feteletseng, botenya ba mpeng, lefu la tsoekere la mofuta oa II, ho eketseha ha lefu la pelo, le ho shoa. Re fihlile mothating ona ka ho hlalosa liphello tsa lipatlisiso mabapi le ho sebetsana le matla a matla a matla a matla, CRF e bohareng, le liphello tsa phekolo e matla le e sa foleng ea khatello ea kelello le glucocorticoid (GC) ka likhoto tse sa tsitsitseng le tse sa tloaelehang.

Setšoantšo sa 1. 

Mekhoa e emelang liphello tse bohloko le tse sa foleng tsa GC ho sebetsa ho axis ea HPA. Litholoana tsa kankere li hlaha kapele, ka metsotso e seng mekae ho feta lihora tse 'maloa ka mor'a khatello ea kelello; Li-GC li sebetsa ka ho toba bokoeng le pituitary mohlomong ka mekhoa ea ho nongenomic. E ncha ...

Litholoana tsa GC mosebetsing oa HPA: o hloekileng le o sa foleng

GC ea kankere-e thibelang maikutlo ea sekhetho sa adrenocorticotropin (ACTH) e latelang e bontšoa habonolo, ka hare ho 18 h pele le khatello ea kelello. Tlhaloso e matla ea maikutlo e hlaha ka bokopi le pituitary (Feie. 1 Ka ho le letšehali), mohlomong ka mekhoa e metle (). Leha ho le joalo, tlas'a khatello ea maikutlo e sa khaotseng, kapa nako e telele ka mor'a hore ho be le khatello e le 'ngoe ea matla (), ho na le ho fokotseha ho khetholloang ha matla a tlhahiso ea likarolo tsa tlhahiso-pele ea kokoana-hloko ea kokoana-hloko, empa e seng ea motheo, ho thibela ACTH (Feie. 2 le refs. 'me ). Ka mor'a nako ea pele ea 24-h ea ho qaleha ha khatello ea kelello e sa foleng, liphello tse tobileng tsa nako e telele tsa li-GC tse boholong li tla thusa "mochine o sa feleng oa khatello ea maikutlo" 'me ka tsela eo o fetole mekhoa e sa tšoaneng e amanang le ho sebetsana ka katleho, botšepehi le basebeletsi ba eona ba maiketsetso. Ke liphello tse sa tobang ka ho fetisisa tsa li-GC tse phahameng tse sa tloaelehang (ho sebetsana ka matšoao a khalase ea matšoao a mpeng) e thibelang pontšo ea mokokotlo o sa feleng oa khatello ea maikutlo (Feie. 1 Right). Ka hona, ho na le mekhoa e meraro ea liketso tsa GC tse bohlokoa nakong ea khatello ea kelello: li-canonical, tse sa foleng le tse sa foleng tse sa tsebeng. Re fumana hore mokhoa ona o mocha o sebetsang o hlalosa liphello ho batho ba imetsoeng kelellong, ba tepeletseng maikutlo, ba nang le lithethefatsi, kapa ba nang le mathata a ho ja.

Setšoantšo sa 2. 

Likokoanyana tse pepesetsoeng ke khatello ea kelello e sa foleng, ho na le mekhoa e phahameng ea GC ho hlohlelletsa likarabo tsa ACTH moqapetsong oa libuka. Litoeba tse sa tloaelehang li ne li tšoaroa ka li-pellets tsa B 'me li ne li bolokiloe mocheso oa motsoako (line e tiileng, letšoao le bulehileng) kapa serame ...

Khatello ea Kelellano e sa Feleng

E fokolang (mohlala, sheba ref. ) likarolo tsa mokokotlo o sa feleng oa khatello ea maikutlo (Feie. 3) li thehiloe ho bapisa palo ea linomoro tsa cell-c immosoreactive tsa c-Fos tse nkoang tse sa tsebeng letho kapa tse sa tsitsang tse hlahelletseng khatello ea maikutlo e bontšitsoeng Feie. 2. Mohlala ona o boetse o na le ts'ebetso ea mohopolo e lulang kapa e lokelang ho feta nuclei (PVN) e hlahang ka thalamus (-), hobane liso kapa taolo ea mohaho ona li ama likarabo tsa ACTH feela linthong tse hatellang. Ho hiroa ha marang-rang ho ka etsoa ka liketso tsa li-neurone ka katleho ea thalamus e bolokang glutamate, e tsejoang ho matlafatsa li-synaptic link (, ). Basomedial, basolateral, le nuclei e bohareng ea amygdala le tsona li ekelitse linomoro tsa cell-c tse ntseng li thibetsoe tse nang le mokokotlo oa khatello ea serame, ha li bapisoa le litoeba tse sa thibeloeng tse nang le bokooa. Amygdala e bonahala e le motsoako oa bohlokoa ka ho fetisisa oa khatello ea kelello e sa foleng, ka lebaka la ho hlokomeloa ha eona ka tsela e tebileng ea likarolo tsa cortical, subcortical, le tsa brain, le karolo ea eona ea bohlokoa ho ho hokahanya mohopolo ().

Setšoantšo sa 3. 

Mokhoa o fokolang o sebetsang oa sethaleng se sa feleng sa khatello ea maikutlo. Mohlala ona o thehiloe mekhoeng e bontšang palo e eketsehileng ea lisele tsa c-Fralabeled ka lebaka la thibelo e thata, e ncha ea li-rats le likheo tsa mariha tse fetileng ha li bapisoa le likhoto tsa naive ( ...

Ho tloha ho li-amygdalar neurons tse sebelisoang ke khatello ea kelello, ho ka khoneha ho hlahisa liketso tsa boitšoaro, likoloi le li-neuroendocrine tse hlahisang khatello ea kelello e sa foleng ka ho fana ka CRF (-). Ho feta moo, li-implants tsa corticosterone (B) tse ka holim'a nuclei e bohareng ea amygdala e eketsa polelo ea CRF mRNA le boitšoaro bo tšoanang le ba ho tšoenyeha () le ho eketsa meriana ea CRF meleng ea hypothalamic PVN, ho thusa likarabo tsa ACTH le B ho ea khathatsong e matla (). Ntle le ho eketseha ha tonate ho potoloha ha B, karolo ea HPA ea methapo e sa feleng ea khatello ea maikutlo e sa sebetsane (Feie. 2;; le ref. ). Ho eketseha ha Corticosteroid e bakoang ke li-CRF tsa amygdalar ke tsa bohlokoa mosebetsing oa marang-rang. Karolo e 'ngoe ea keketseho ea PVN (mpPVN) e nang le mefuta e mengata e ka' nang ea e-ba le litlhahiso tse thibelang ho thibela (GABA / CRF) liphateng tsa bethe tsa stria terminalis () e bonahalang eka e thibela ketsahalo ea CRF kamoreng ea bethe ea stria terminalis (). Ho kenya letsoho ka makhetlo a mabeli ho thibela li-CRR neurons ka mpPVN ho ka etsa hore (ho thibela) boitšoaro bo botle, boiponelo le li-neuronic neurons. C-Fos lisele tsa lisele li ile tsa eketseha PVN likarolong tse sa tsitsang tse nang le khatello ea maikutlo, ha li bapisoa le taolo ea bokhopo (). Mekhoa e meng ea maoto ho mpPVN e ka boela ea eketsa tšireletso ea CRF linthong tse nang le khatello ea kelello e sa foleng ().

Lisele tsa CRF li-amygdala hape li na le monoaminergic neurons tse sa tšoaneng tse sa sebetsaneng. Sebakeng sa locus coeruleus (LC), CRF e eketsa litekanyetso tsa basal ho thunngoa ha LC neurons le ho pateloa ha norepinephrine ho forebrain (), mohlomong ho eketseha ho tsosoa le tlhokomelo. Ho feta moo, karabo ea motlakase ea LC ho hypotension e hloka phallo ea amygdalar CRF, 'me likarolo tse sa tsitsitseng tse ntseng li hatelloa li ekelitse molumo oa CRF ka LC (, ). Ketsahalo ea li-nerotoninergic neurons ho raphe ea matšoao e tšoaroa ke CRF le khatello ea kelello (-). LC ka bobeli le rase ea dorsal e ne e e-na le likarabo tse kholo tsa c-Fos linthong tse sa tsitsang tse ngata ho feta likokoanyana tse nang le boitsebiso bo nang le khatello ea maikutlo e thata-kholo (). Le hoja li-GC tsa systemic li thibela ho sebelisoa ha LC linthong tse sa tloaelehang, sena se ka 'na sa e-ba ka lebaka la liketso tsa bona tsa ho lokisa le ho se na liphello tse tobileng ho LC neurons.

Liphello tsa Ts'ebetso tsa GC

Ha corticosteroids e ntse e eketseha, ho na le likamano tse matla tse pakeng tsa maemo a tsitsitseng a 'mele le boima ba' mele le bokhoni ba caloric (Feie. 4 Top). Joalokaha ho tsebahala ho tsoa ho bakuli ba nang le lefu la Cushing's, ho tsepamisa mohopolo ho GC maemong a khatello ea maikutlo ho bokella pheriferale ea amino acid ho tsoa mesifa le mafura a acids le glycerol ho tsoa mabenkeleng a mafura a pheriferale ho fana ka mafura bakeng sa tsoekere ea tsoekere ka sebete (). Li-rats, maemo a phahameng a li-GC a thibela ho phalla ha hormone, ho fokotsa khōlo e nyenyane, le kutloelo-bohloko ea neural outflow, ho fokotsa mefuta e meng ea mafura (-). Feie. 4 e bonts'a liphello tse tsoang ho likhoto tse tloaelehileng tse nkiloeng ke li-concentrated B tsa matsatsi a 5 le ho lumelloa ho noa sucrose ad libitum (). Ho na le kamano e ntle pakeng tsa B le ho tlosa ho kenngoa ha lijo le mafura a B le mesenteric (Feie. 4 Bohareng bo Hare 'me Ka tlaase ho le letšehali). Ka lehlakoreng le leng, ho ne ho se ke ha e-ba bonolo ho ja lijo kapa mahlaseli a maholo a mafura a mafura a neng a amehile ke B (Feie. 4 Hantle Bohareng 'me Ka ho le letšehali). Ka hona, likhahla tse ngata tsa B tse kenang khatellong ea likokoanyana li boetse li fana ka matla a bolokiloeng ho ea ho ajoa ha 'mele (). Ho hanyetsa insulin e hlahang ka holimo B e ka 'na ea e-ba phello ea likarolo tsa li-GC, ho e-na le li-peripheral. Leha ho le joalo, ho tsosolosoa ha insulin ho pata ka B ke habohlokoa bakeng sa ho bolelloa ha lichelete tsa matla. Ha ho se na insulin, ts'ebollo ha e hlahe (). Ho imeloa kelellong hangata ho fokotsa ho noa ha likokoanyana, 'me ho hloka taolo ea bobeli, botenya bo boholo bo thata ho bontša (). Ha ho sebelisoa lisebelisoa tse fepehileng, li-rats tse nang le li-GC tse ngata tse nang le matla a mangata li na le li-depot tse ngata tsa mesenteric (). Ka lebaka leo, ha ho se na khatello ea likamano, li-GC li hlahisa botenya bo tebileng ka ho senyeha ha mokhoa o itseng. Ka nako e ts'oanang, ho koahela mahlaseli a plasma B ea 12-15 μg / dl ho hlahisa mRNA ea CRF ka amygdala le ho e thibela mpPVN (, ). Hoa thahasellisa hore likhoto tse nang le libaka tsena tsa B ha li amohele likhatello, ntle le haeba li kile tsa hatisoa pele, tse ka amanang le mesebetsi ea sehopotso ea nuclei e tloaelehileng ea thalamus (Feie. 2 le ref. ). Ka mokhoa o ts'oanang, bakuli ba Cushing's syndrome ba sa tlaleheng maikutlo a khatello ea maikutlo le bona ba bontša ho fokotsa ho arabela ha khatello ea maikutlo.

Setšoantšo sa 4. 

B e boetse e fana ka mabenkele a matla ho libaka tsa malapa 'me e eketsa lijo tsa sucrose. Litoeba tse khethiloeng ke 'mele li ile tsa nkeloa sebaka ke mefuta e mengata ea B le ho lumelloa ho noa sucrose bakeng sa matsatsi a 9 ka letsatsi la liteko tsa 15 (). Ntho ea bohlokoa haholo ...

Sucrose Ingestion le Central B ka Rats e khethiloeng

Kamora 'meriana le ho tlosoa ha GCs, ho ja lijo ho fokotseha, joalo ka ha tekanyo ea boima ba' mele (mohlala, Feie. 4;; refs. 'me ). Leha ho le joalo, ha litoeba tse nang le khethollo li fanoa ka sucrose (30% tharollo) ho noa ho phaella ho saline, liphoofolo li noa ≈40% ho feta li-sucrose e le lithibelo tsa sham-adrenalectomized (), mohlomong ka lebaka la ho fokotsa tšusumetso. Ho makatsang ke hore lipōli tse nang le lithethefatsi tse noang srorose li ile tsa tsosolosa boima ba 'mele, lijo tsa lijo, li-depot tse mafura, le litebelisoa tsa mahlaseli a mahlahahlaha a sootho a tloaelehileng a tloaelehileng. Ho fokotsa lik'hemik'hale tsa liprotheine ka mahlaseli a sootho adipose, tekanyo ea ho tsoa ka kutloelo-bohloko, li boetse li fokotsehile ho tloaelehile, ha li bapisoa le likhooe tsa metsi tse nooang metsi tse nooang (). Tlhahlobo ea lipotoloho tse tšoanelehang tsa HPA tsa liphala li bontšitse hore ho noa ho noa ho tlosa khatello ea maikutlo ea CRR mRNA ka har'a amygdala le ho thibeloa mRNA ea mantlha ea mpa ea motlakase ho mpPVN. Ha e le hantle, ho ne ho e-na le kamano e matla e fapaneng pakeng tsa palo ea sucrose e neng e sebelisoa letsatsing la ho qetela la teko ea 5-day le CRR mRNA ka mpPVN (). Ho phaella moo, ho noa sucrose ho boetse ho thibela ho phahama ha dopamine-β-hydroxylase mRNA ka lik'hemik'hale tse ling tsa A2 / C2 nucleus ea tractus solitarius le LC (). Liphello tsena li fana ka maikutlo a hore haeba matla a lekaneng a lokisoa ka ho kenngoa ka boithaopo ho lik'hilojule tse monate, litlolo tsa metabolism le neuroendocrine tse bakoang ke ho ba sieo ha B disappeared. Tlhaloso ena e matlafatsoa ke hore litoeba tse khetholloang li noa haholo ha li noa li-saccharin tse lekanang haholo 'me li bonts'itse ho fokotseha ha CRF ea amygdalar le ho phahama ho li-CRF tse ntseng li hlokomeloa ka mor'a hore li-adrenalectomy (, ).

B e ka 'na ea itšoara ka tsela e ts'oanang le hore e tsoele pele ho potoloha ho potoloha, kapa ho tšoana, potoloho ea boko. Ho leka sena, re kentse B ho boko (100 ng / letsatsi bakeng sa matsatsi a 6) lipotsong tse sa tloaelehang tse neng li lumeletsoe sucrose le / kapa saline ho noa (). Tlas'a maemo a mabeli, bohareng ba steroid infusion bo tsositse CRF peptide ka PVN le ho khutsisa ha ACTH, ho feta liphello tse thibelang li-sucrose (). Ho feta moo, ha linotši tse nooang li-sucrose li ne li kenngoa ka hare ho B le ho thibeloa ka makhetlo, ho ile ha etsoa likarabo tsa ACTH ka letsatsi la boraro la thibelo ho bapisoa le litoe tse neng li kenngoa ka hare ho saline (). Ho totobetse hore B e kenngoa ka ho toba bokong ha e thibe empa ho e-na le ho thabisa boitsebiso ba ACTH bo bakoang ke khatello ea kelello. Liphuputso tsena li matlafatsa tlhaloso ea hore li-GC li fana ka maikutlo a sa foleng a sa lekaneng a tsoang ho pota-pota, athe e ba le menyetla e sa tloaelehang bokong.

Bopaki ba liphetoho tse matla tsa meriana tse kopanetsoeng ke B bo re etselitse ho batlisisa mehloli ea eona e ka hlahang. Ho hlahlojoa ha boitsebiso bo tsoang liphuputsong tsa rona tse fetileng tse tlalehiloeng kapa tse sa hatisoang hape ho bontšitse kamano e matla haholo pakeng tsa palo ea sucrose e jang le CRF mRNA PVN (Feie. 5 Ka ho le letšehali). Data e boetse e bonts'a ho hokahanngoa ha bohlokoa le ho tsitsitseng pakeng tsa mesenteric fat mass le mmele oa CRF PVN (Feie. 5 Right). Lintlha tsohle tse bontšitsoeng ho Feie. 5 li tsoa linthong tse sa tloaelehang tse sa sebelisoeng B, ho noa kapa sucrose kapa saccharin ho phaella ho saline, kapa saline feela. Leha ho le joalo, thupelong e 'ngoe le e' ngoe eo re nang le litekanyo tsa mesente ea fatše ea mesenteric hammoho le hypothalamic CRR mRNA, e tsoang ho khethollo e sa tloaelehang kapa ho tswa ho likhoto tse sa tšoaneng, ho na le kamano e sa lumellaneng le e khōlō pakeng tsa mesenteric fat weight le polelo ea CRF ho PVN. Ka lehlakoreng le leng, ha ho na kamano pakeng tsa boima ba mafura a fatše le CRF mRNA kahare ho PVN ho teko leha e le efe (data e sa bontšoang). Liphello tsena li bontša ka matla hore mabenkele a mesenteric (empa ha a sc) a sebetsa e le letšoao la mabenkele a matla a matla a fepa ho thibela mosebetsi oa CRF ka har'a axi ea HPA.

Setšoantšo sa 5. 

Bobeli ba sesepa sa sucrose le metsi a mesenteric haholo, ha se amane haholo le CRR mRNA PVN. Lintlha tsohle li tsoa lintlheng tse sa tšoaneng tse nang le B tse ileng tsa fuoa sucrose kapa saccharin. Dintlha tsa sucrose li tsoa ho refs. ...

Ka ho feletseng, liphuputso tsena li khothalletsa mokhoa o mocha oa liphello tse sa foleng tsa corticosteroid tse bontšitsoeng Feie. 1 Right. Bokong, li-GC tse sa foleng li fepa pele ho tsosolosa li-axis tsa HPA. Sebakeng se ka thōko, li-GC li etsa hore ho be le lisebelisoa tse ngata tsa matla a mesenteric. Mabenkele a maholo a matla (a bontšitsoeng ke mesenteric WAT mass) a fana ka pontšo e sa tsejoeng ea maikutlo ho bokong ho fokotsa tšebetso ho axis ea HPA. Feie. 6 e bontša mohlala oa rona oa ho sebetsa ha maikutlo a ts'ebetsong bokong. Ha lesole le hlahisitsoeng ka matla a mpeng le ntse le eketseha, lisele tse mpe tsa lisele tsa A2 / C2 tsa mahlaseli a marang-rang tse ka har'a mokokotlo oa tractus solitarius li fokotsa ho sebelisoa ha li-enzyme tse hlokahalang bakeng sa catecholamine synthesis; sephetho sena se boetse se etsahala ho A6 (LC). Pontšo e fokotsehileng ea noradrenergic ho mpPVN (), ka lehlakoreng le leng, e fokotsa ts'ebetso ea CRF le secretion. Ka hona, ho na le matla a matla a ho hlahloba maikutlo a CRF ho PVN. Letšoao le ts'oanang le matla a ho thibela matla a mpa ha le bonahale le ama MRNA ea CRF ka amygdala.

Setšoantšo sa 6. 

Mokhoa o fokolang o sebetsang oa liketso tsa B ka maikutlo a metsoako ea CRF le secretion ea ACTH. Ka pel'a ho ja lijo le ho boloka insulin, B e susumeletsa matla a matšoao a matla a mpa. Ka lehlakoreng le leng, ntle le ho ja lijo tse lekaneng le ho boloka insulin, ...

GCs Act on Brain ho eketsa Matla a Stimulus

Phello e 'ngoe ea bohlokoa ea li-GC ho tsamaiso ea methapo ea mantlha e bonahala e le ho eketsa liketso tse qobelloang tsa mesebetsi e meng. Ho hlakile hore sena ke 'nete bakeng sa mekhoa ea ho sebelisa lithethefatsi (, ), empa e boetse e bonahala e le 'nete bakeng sa liketso tse ling tse sa sebetseng. Mekhoa e tloaelehileng, e tsitsitseng ka boithatelo e sebelisa mechine e tsamaeang ka mabili 'me e tla tsamaea lik'hilomithara bosiu bo bong le bo bong, ha likhooe tse sa sebelisetsoeng li sa sebelise mabili, ntle le hore li nkeloe sebaka ke dexamethasone (). Ho matha ho ile ha khutlisetsoa linthong tse sa tloaelehang tse lekanang le tekanyo ea phekolo ea B, 'me likhahla tse phahameng tsa steroid tse neng li ka sebetsana le bokooa ba GC, li ne li hlokoa hore li sebetse ho finyella litekanyetso tse hlokometsoeng ka litoeba tse sa tšoaneng (). Ka ho tšoanang, litoeba tse tsitsitseng li noa sesebelisoa se sengata sa lijo, athe ratsana tse nang le litlhare tse nooang li noa haholo. Ka bobeli li tsitsitse ha li kena (Feie. 7 le ref. ). Hape, ka ho nkeloa ha R litoeba tse ntseng li eketseha, ho kenngoa ha saccharin ho eketsa ka mokhoa o tsitsitseng oa tefo, 'me ho hloka hore motho a be le litekanyetso tse phahameng tsa steroid ho tsosolosa ho noa ka likhoto tse sa tloaelehang ho batho ba fumanoang linthong tse sa tšoaneng (). Re sa tsoa fumana ts'ebetso e tšoanang e amanang le tekano ea B ka likhoto tse ratoang ka boithatelo ho kenyelletsa likokoana-hloko; boemo bo phahameng ba steroid bo hlokeha ho tsosolosa lijo tse nang le mafura ho litekanyo tse hlokometsoeng lipotong tse sa tšoaneng (SELF le MFD, data e sa hatisoang). Ka hona, joaloka liphello tsa B ho noa sophose, empa ho se je lijo (Feie. 4), maemong a khatello ea B a eketsa ts'ebetso ea seo ho ka thoeng ke "lijo tsa matšeliso," ke hore, lijo tse natefisang, litšoaneleho tse utloahalang tse bontšang lik'halori.

Setšoantšo sa 7. 

B e eketsa sebete sa seno se monate, saccharin. Litoeba tse tsamaisoang ka letsoho kapa tse nang le mefuta e mengata ea phekolo ea mefuta e sa tšoaneng li ile tsa lumelloa ho noa saccharin bakeng sa matsatsi a 9 matsatsing a teko ea 15. Lintlha tse bontšitsoeng li emela ho noa letsatsing la ho qetela la teko ...

Ha karabo e amanang le B-saccharin e hlahlojoa lipakeng tsa ADX, boima ba mafura a mafura le a mesenteric, le hoja ho ja lijo ha ho joalo. Ka lehlakoreng le leng, ha matšeliso a lijo a phekola (sucrose le likokoana-hloko), mesenteric empa e se sc fat mafura a eketseha ka boima ka ho eketseha B maqhubu (Feie. 4). Matšeliso ana a khotsofatsang a bakoa ke litšenyehelo tsa ho ja lijo tse hlahisitsoeng ke likhoto tse nang le bothata bo botle bo hlahisitsoeng ke B ka ho toba ho "ventricle" (cerebral ventricle)). Liphello tse tšoanang li etsahala ka likhopo tse sa tsejoeng tse nang le khatello ea kelello e sa feleng: serrose e eketsehileng e kenngoa serame, empa ho ja lijo tse nyane, hafeela likhahla tsa B li le boemong ba khatello ea kelello e fumanoang ke boko ba GC receptors ().

Liteko tsa ba bang li boetse li fana ka maikutlo a hore polelo e kholo ea CRF ka mor'a khatello ea kelello e fokotsehile ka tlhahiso ea lijo tse khethiloeng. Li hlahisitsoe ke paradigm e nang le khatello e fapaneng e nang le matla a mangata a phahameng (lijo tse phahameng tsa sucrose le mafura) bakeng sa matsatsi a 30, likhoto tse hanelang ho nona haholo lijong li ne li phahame moriana oa CRF ho PVN, athe lino tse nang le bothata bo bakoang ke ho ja haholo ha li bontše CRF (). Ho feta moo, likhoto tse pepenene le mohatla o ke keng oa qojoa 24 h pele teko ea ho thibela bo-shuttle e sebetse ho feta ho laola. Leha ho le joalo, haeba ba noa tharollo e tsoetseng pele ea dextrose nakong ea bosiu ka mor'a tšabo e ke keng ea qojoa le ho boloka boima ba 'mele le boima ba' mele ea bona, ba ne ba tšoana le likhoto tse laolang feela (). Mokhoa ona oa ho thibela lefu o ne o sa hlokomeloe haeba ho sa noe nonnutritive saccharin ho ile ha lumelloa (, ).

Ha li ntse li kopanngoa, liphuputso tsena li bontša ka matla hore litekanyetso tsa likhatello tsa li-GC li sebetsa bokong ho eketsa matla () mesebetsi e amanang le ho batla (mohlala, tsamaiso ea likoloi), ho hlophisa likarabo tsa ho itšireletsa, le ho fetola likarolo tse ling tsa phepo ea phepo ea mmele (sucrose le mafura). Ho feta moo, ba bonts'a hore likhahla tse phahameng tsa B li baka phepo ea matšeliso ha likokoanyana li hatelloa ka nako e le 'ngoe. Ka hona, matlo a mararo a sa foleng a li-GC ke ho eketsa mosebetsi oa CRF mokokotlong o moholo oa amygdala, ho eketsa botumo bo matla bo matla, le ho eketsa botenya ba mpeng, e leng se eketsang pontšo ea maikutlo a thibelo ea metsola ea meriana oa CRF ka mpPVN le ho fokotsa mosebetsi oa HPA. Ho iphetola ha lintho, lipotoloho tse kholo tsa boko li inehetse ho lula li phela 'me li fumana lijo le balekane. Maemo a mangata a holimo a li-GC a sebetsa ka litsela tse tharo tse sebetsang hantle ho tse peli ho tsena. Ba finyella boikarabelo bo tsitsitseng boemong ba boitšoaro bo botle, bo ikemetseng le ba mantlha ba sekolo se sa foleng sa khatello ea maikutlo, ha ba ntse ba boetse ba tsosolosa bothata ba ho fumana mokhoa oa ho tsoa bothateng, le ho fokotsa ts'ebetso e tsoetseng pele ka ho hlahisa matla a matla a mpa.

Na Liphello Tsa Khatello ea Kelello le Li-GC tse Ntle ho Likotla li Sebelisetsoa Batho?

Re lumela hore karabo ea potso ena ke "e!" E hlakileng. "Li-syndromes tse sa tšoaneng tsa ho ja [bulimia le lefu la ho ja bosiu ()] li na le lik'hilojule tsa ho ja lijo tse ngata ka ho itlopa joala. Ba nang le bothata ba ho ja, ebang ke ho itlopa lijo kapa ho ja lik'hilojule tse ngata tsa lefifi bosiu, ka kakaretso ba iponahatsa ba le khatello e sa khaotseng (, ) 'me li bobebe. Lijo tse haelloang haholo-hangata li na le mafura a mangata le lik'habohaedreite tsa caloric 'me li ka' na tsa hlalosoa e le matšeliso a lijo. Lipalo tsa GC ho bakuli bana li hanyenyane empa ha li phahame haholo (, ). Ka lehlakoreng le leng, bakuli ba nang le anorexia nervosa ba na le maqhubu a phahameng a cortisol haholo 'me ba na le maemo a tlase a insulin haholo empa ba ntse ba e-na le karolelano e fokolang ea sc ho ea mabenkeleng a mafura ka mpeng joalokaha ho bontšoa ke computed tomography (, ). Litefiso tse phahameng tsa ho tepella maikutlo li fumanoa lihlopheng ka bobeli. Ho bonahala ho ka etsahala hore phapang e kholo pakeng tsa li-syndromes tse sa tšoaneng le anorexia nervosa ke hore batho ba nang le mekhoa ea pele ba leka ho etsa hore ba ikutloe ba le betere ka ho fokotsa mesebetsi ea CRF ea hypothalamic ka ho eketsa pontšo ea bona ea maikutlo a bobebe. Leha ho le joalo, li-anorexics li ka 'na tsa koaleloa ho batla kapa ho phonyoha mekhoa ea phenotype ea tšohanyetso e amanang le tlala. Ho tla ba monate ho fumana hore na li-GC tse ka tlase ho batho ba nang le mathata a sa tsitsang le anorexia li bonahatsa ho hatelloa ho hlahisoang ke phepo ea motsoako oa HPA. Ho itšetlehile ka mohlala oa rona, ho ja lijo tsa matšeliso ho ne ho tla lebelloa ho fokotsa tšebetso ho li-axis tsa HPA.

Mokhatlo oa American Psychiatric Association's Diagnostic and Statistical Manual IV o thathamisa lintlha tse robong, tseo tse hlano tsa tsona li lokelang ho fihlelleha, bakeng sa tlhahlobo ea khatello ea maikutlo. Ho tsena, lihlopha tse tharo li fapana ka bobeli: boima ba 'mele / boima ba' mele, hyperphagia / hypophagia, le hypersomnolence / boroko. Ka kakaretso, motho oa pele oa bobeli o tsamaea le ts'oaetso ea "khatello ea maikutlo," athe ea bobeli e tsamaea le ts'oaetso ea "khatello ea maikutlo", ). Basali ba bacha, lihlopha tsena ka bobeli li phahame ka mokhoa o fokolang feela oa ACTH le li-cortisol (). Leha ho le joalo, ho batho ba seng ba hōlile ba tepelletseng maikutlong le bathong ba seng ba hōlile le ba batšehali, axisisi ea HPA e khathatsoa, ​​haholo-holo ho ba nang le bothata ba ho tepella maikutlo (-). Ho feta moo, mefuta e mengata ea methapo ea meriana e tsoang ho bakuli ba nang le bothata ba ho tepella maikutlong le ho qhibiliha ha maikutlo ho bontša hore batho ba nang le khatello ea kelello ha ba na li-CRF le tsa catecholamine,, , ). Hape, ho ka 'na ha etsahala hore ebe ba fokolang boima ba' mele, ba ja haholo, 'me ba robala haholo ha ba tepeletse maikutlo [kapa ba tšoenyehile ()] ba leka ho ikutloa ba le betere ka lijo tsa matšeliso. Hoa tsosoa hore phello e sa batleheng ea lithethefatsi tse loantšang maikutlo ke botenya haholo ().

Le hoja mehlala e boletsoeng ka holimo e bontša hore batho ba nang le lefu lena la mafu a kelello ba ja haholo ha ba hatelloa, ha ho hlokahale hore ba be le mathata a feteletseng a kelello ho sebelisa matšeliso a matšeliso ha ba ikutloa ba theohile tlaase. Linaheng tse tsoetseng pele haholo, sena ke ketsahalo e amohelehang hantle le e tloaelehileng, e leng seoa se bakoang ke ho nona haholo (). Ha ho pelaelo hore ho ja lijo tse ngata tse ngata le lik'habohaedreite li tšelisa batho 'me li ka etsa hore ba ikutloe ba be ba sebetse hantle (). Ho batho, ho ikutloisa hamolemo ho ka 'na ha fella ka ho tšoana le likhoto, ho fokotseha ho boleloa ka har'a CRF le dysphorias e hlahisoang. Leha ho le joalo, mokhoa oa tloaelo oa ho sebelisa lijo tsena, mohlomong o tsositsoe ka ho tloaeleha ho hoholo ha cortisol ka lebaka la ho imeloa kelellong, ho fella ka botenya ba mpeng. Ka bomalimabe, mofuta ona oa botenya haholo o amahanngoa le lefu la tsoekere la mofuta oa II, lefu la pelo le lefu la stroke. Nakong e khutšoanyane, kapa lichabeng moo ho sa fumanehe lijo tsa matšeliso hang-hang le ka nako e telele, nako le nako khatello ea matšoenyeho ka lijo tse monate kapa tse mafura e ka 'na ea e-ba molemo. Ka tloaelo ho leka ho loantša mathata a bakoang ke khatello ea kelello ea setseishene se ka sehloohong sa khatello ea kelello ea CRF se sithabetsang se ka etsa hore motho a ikutloe a le betere, empa ho ka etsahala hore e be bobe bakeng sa bophelo bo botle ba nako e telele.

lumela hore baa fokola

Re leboha Drs. Kim P. Norman le Larry Tecott (Lefapha la Psychiatry, Univesithing ea California, San Francisco) bakeng sa ho kenya letsoho. Mosebetsi ona o ne o tšehetsoa ka karolo e itseng ke Mokhatlo oa Sechaba oa Mokhatlo oa Bophelo DK28172 le Lefapha la Tlhahlobo ea Lipatlisiso le Allocation Committee (REAC) e tsoang Univesithing ea California, San Francisco. NP e tšehetsoa ke Mekhatlo ea Sechaba ea Bophelo bo Fanang ka Bophelo F32-DA14159, SElF e tšehetsoa ke Mokhatlo oa Fellowship ho tswa ho Dutch Diabetes Research Foundation, mme HH e tšehetsoa ke Mekhatlo ea Sechaba ea Health Grant F32-DA14143.

Notes

Likhaloso: ACTH, adrenocorticotropin; B, corticosterone; CRF, motsoako oa ho hlahisa corticotropin; GC, glucocorticoid; HPA, hypothalamo-pituitary-adrenal; LC, locus coeruleus; PVN, nuclei ea maiketsetso; mpPVN, PVN e kholo; WAT, lihlahisoa tse tšoeu tsa adipose.

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