Li-androgen receptors tsa membrane li ka 'na tsa lumellana le androgen ho matlafatsa. (2010)

Psychoneuroendocrinology. 2010 Aug; 35 (7): 1063-73. Epub 2010 Feb 6.
 

mohloli o moholo

Lefapha la Cell & Neurobiology, Keck Sekolo sa Bongaka, Univesithi ea Southern California, Los Angeles, CA 90033, USA.

inahaneloang

Tlhekefetso ea Anabolic-androgenic steroid (AAS) e atile. Ho feta moo, AAS ea matlafatsa, joalo ka ha ho bonts'oa le boits'oaro ba litoeba. Leha ho le joalo, li-receptors tse fetisang litlamorao tse matlafatsang tsa AAS ha li hlake. AAS e kanna ea tlama ho li-receptor tsa khale tsa androgen androgen (recs) kapa li-membrane receptors. Re sebelisitse mekhoa e 'meli ho hlahloba karolo ea li-AR tsa nyutlelie ho tsamaiso ea boithati ba AAS. Taba ea pele, re ile ra leka ho itaola ha andro ka likhoto ka testicular feminization mutation (Tfm), e kenang le androgen binding. Haeba lihlahisoa tsa matla a nyutlelie li bohlokoa bakeng sa boits'oaro ba AAS, banna ba Tfm ha baa lokela ho ikenya hape. Ba batona ba Tfm le mofuta oa hlaha (WT) ba iphelisa ka tsela e seng aromatizable androgen dihydrotestosterone (DHT) kapa koloi intracerebroventricularly (ICV) ka li-ratiine tsa (FR) tse tsitsitseng ho FR5. Ka bobeli likotlo tsa Tfm le WT li fumane khetho bakeng sa ts'ebetso e sebetsang ea nko nakong ea tsamaiso ea DHT (66.4 +/- likarabo tsa 9.6 / 4 h bakeng sa Tfm le 79.2 + /- 11.5 bakeng sa likarabo tsa WT / 4 h), le likhapha tsa nko li ile tsa eketseha ha li ntse li eketseha. Tlhokahalo ea FR e eketsehile. Lits'oants'o tsa likhetho li ne li le tlase haholo ho likoloi tsa tsamaiso ea likhoto (42.3 +/- likarabo tsa 5.3 / 4 h bakeng sa Tfm le 19.1 +/- likarabo tsa 4.0 / 4 h bakeng sa WT). Re boetse re lekile ho itaola ha DHT e kopantsoeng le bovine serum albin (BSA) C3 le C17, e lekantsoeng ke liketso tse ka seleng ea sele. Hamsters ba ile ba lumelloa ho itaola ka bobona DHT, BSA le DHT-BSA ka matsatsi a 15 ho FR1. Li-hamsters li bontšitse khetho e kholo bakeng sa likarabo tsa DHT (18.0 +/- 4.1 likarabo / 4 h) kapa li-DHT-BSA conjugates (10.0 +/- likarabo tsa 3.7 / 4 h le 21.0 +/- 7.2 + / 4 +) Likarabo -2.5 likarabo / 2.4 h). Ha li kopantsoe hammoho, lintlha tsena li bonts'a hore li-AR tsa nyutlelie ha li hlokehe bakeng sa ho itaola le androgen. Ho feta moo, tsamaiso ea androgen e ka tsamaisoa ke li-receptor tsa plasma membrane.

Copyright 2010 Elsevier Ltd. Litokelo tsohle li sirelelitsoe.

Keywords: Li-anabolic le androgenic li-steroid, ho itaola, ho amohela lisele tsa androgen, receptor ea nyutlelie le ea tlhaho

Anabolic-androgenic steroids (AAS) ke lithethefatsi tsa tlhekefetso. Lintho tsena tse tsoang ho testosterone (T) li sebelisetsoa merero ea lipapali le botle ba (Yesalis et al., 1993). Litla-morao li tsoa ho hypogonadism le gynecomastia ho ea ho pelo le dysfunction ea hepatic (Leshner, 2000). Ntle le moo, bopaki bo ntse bo bokella hore tlhekefetso ea AAS e baka liphetoho tsa maikutlo (Mopapa le Katz, 1994), mabifi (Choi le Mopapa, 1994, Kouri et al., 1995), hape e ka hlahisa ho itšetleha (Brower et al., 1991, Brower, 2002). Leha ho na le matshwenyeho a ntseng a hola, mecha ea tlhekefetso ea AAS ha e utloisisoe hantle.

Ho batho, ho boleloa hore ho qalisoa ha tšebeliso ea AAS ho susumetsoa haholo ke litlamorao tsa anabolic, empa ba bang ba ba hlekefetsang qetellong ba hlaolela ho its'epaha (Brower, 2002). Bopaki bo tsoang lipatlisisong tsa liphoofolo bo tšehetsa khopolo ena. AAS e beha boikhethelo ba sebaka (CPP) ka litoeba (Arnedo et al., 2000) le likhoto (Packard et al., 1997, Packard et al., 1998, Frye et al., 2002). Ho feta moo, hamsters ka boithaopo a ja AAS ka molomo (Wood, 2002,, intravenous (Wood et al., 2004), le tsamaiso ea intracerebroventricular (ICV)DiMeo le Wood, 2004, Triemstra le Wood, 2004, Wood et al., 2004, DiMeo le Wood, 2006b).

Le ha Ts'ebetso ea ICV e bonts'a libaka tsa bohlokoa tsa ts'ebetso, li-hormone le li-receptors tse sebelisang matlafatso ea AAS ha li hlake. Bopaki ba hajoale bo fana ka maikutlo a hore litlamorao tse matlafatsang tsa T li tsamaisoa ke li-androgens, ho fapana le ka estrogens kamora aromatization. Male hamsters a tla iketsetsa tsamaiso ea dihydrotestosterone (DHT; DiMeo le Wood, 2006b) le li-androgens tse ling tse ke keng tsa qojoa (Ballard le Wood, 2005). Ntle le moo, T-tsamaiso ea T e thibetsoe ke anti-androgen flutamide (Peters le Wood, 2004). Joale potso ea fetoha: na "androgenic sign" e fetisoa joang bokong?

Androgen receptor (AR) ke li-receptor tsa nyutlelie tsa khale tsa nyutlelie tse sebetsang e le ntho ea ho ngola. Li-AR li qhekelletse ka hara meaho e amanang le ts'ebeliso e mpe ea lithethefatsi, joalo ka li-nucleus accumbens (Acb) le sebaka sa likarolo tsa katara (VTA; Simerly et al., 1990, Wood le Newman, 1999). Ho boetse ho na le bopaki ba li-steroid tsa gonadal tse sebetsang ka li-receptor tsa cell cell (Mermelstein et al., 1996, Zhu et al., 2003, Thomas et al., 2006, Vasudevan le Pfaff, 2007).

Thutong ea hajoale, re sebelisitse mekhoa e 'meli ho tseba karolo ea khale ea nyutlelie ea matlafatso ea androgen. Ho fokotsa ts'ebetso e ka khonehang ea li-estrogen receptors (ER), re ile ra leka ho itaola ea DHT. Tekong ea pele, likhoto tse nang le testicular feminization mutation (Tfm) li ile tsa lekoa bakeng sa ho ikarabella ho ICV ea DHT. Tfm ke setsi se le seng se hlahisang li-AR tse nang le phoso tse nang le ligand e fokolang (Yarbrough et al., 1990). Liroto tsa Male Tfm li bonts'a mofuta oa kantle oa mosali ka lebaka la ts'usumetso e sa lekaneng ea androgenic nakong ea kholo (Zuloaga et al., 2008b). Haeba li-AR tsa nyutlelie tse hlokahalang li hlokahala bakeng sa matlafatso ea AAS, likhoto tsa Tfm ha lia lokela ho ipehela DHT. Sebakeng seo, likhoto tsa Tfm li ile tsa khona ho fumana tsamaiso ea boits'oaro ea DHT. Boitekong ba bobeli, re ile ra leka ho itšireletsa ha ICV ea mekhoa ea DHT e sa kenngoeng hantle ka hamsters. Ha DHT e kopantsoe le bovine serum albin (BSA), liketso tsa eona li lumelloa ho li-receptors tsa selefounu. Haeba li-AR tsa nyutlelie li hlokahala bakeng sa ntlafatso ea androgen, li-hamsters ha lia lokela ho itaola ka boeona ho DHT ho kopantsoe le BSA. Ho fapana le moo, li-hamsters li bontšitse khetho e hlakileng bakeng sa DHT e kopaneng le BSA. Ka kopanelo, lithuto tsena li bonts'a hore li-AR tsa nyutlelie ha li hlokehe bakeng sa ho itaola le androgen. Ho fapana le moo, matlafatso ea androgen a kanna a kenelloa ke membrane ARs.

Mekhoa le Lisebelisoa

Lihlooho

Likhoto

Likhoto tsa banna ba baholo ba Tfm le li-mofuta oa hlaha (WT) li fumanoe koloni Univesithing ea State State. Mofuta oa bona oa genotype o netefalitsoe ke PCR, e ts'oanang le mekhoa e hlalositsoeng pele (Fernandez le al., 2003). Ka bokhutšoanyane, likarolo tsa tsebe li ile tsa chekoa bosiu bo le bong ho 55 ° C ka har'a buffer e nang le proteinase K, ebe mocheso o kenelletse 95 ° bakeng sa metsotso ea 30. AR e ne e holisitsoe sebelisa primer ea pele 5'-GCAACTTGCATGTGGATGA-3 ′ mme e khutlisa primer 5'-TGAAAACCAGGTCAGGTGC-3 ′, e hlahisa sehlahisoa sa 135bp. Mehlala e ntlafalitsoeng e ne e se e entsoe ka enjine ea thibelo ea Sau96I (R0165L, New England BioLabs, Ipswich, MA) bosiu ho 37 ° C ebe e tsamaisoa ke li-agarose tsa 3%. Ke WT AR feela e khaotsoeng ka enzyme ena ea thibelo, e siea lihlopha tse peli ka tlase ho 100bp, athe Tfm AR e lula e sa sebetse. Liphoofolo tsa Tfm li ne li boetse li netefalitsoe ke phenotype, ka boteng ba li-nipples, sebaka sa botšehali ba botšehali ba botšehali le liteko tsa ka mpeng. Likhoto tsa Tfm li kile tsa sebelisoa ho bonts'a litlamorao tse seng tsa genomic le androgen ho hippocampus (MacLusky et al., 2006). Qalong ea teko, likhoto tsa WT li ne li le pakeng tsa 75 ho isa ho 140 ea letsatsi, mme litoeba tsa Tfm li ne li le lipakeng tsa 75 ho isa ho 138 ea matsatsi.

hamsters

Li-hamsters tsa banna ba baholo ba Syria (130 - 150 g) li fumanoe ho Charles River Laboratories (Wilmington, MA). Liphoofolo li ne li bolokiloe ka bolulo mokelikeli o khutliselitsoeng (14L: 10D) ka lijo le metsi tse fumanehang ad libitum. Lits'ebetso tsohle tsa liteko li amohetsoe ke tlhokomelo ea liphoofolo ea tikoloho le likomiti tsa tšebeliso ea litsi tse amehang mme li etsoa ho latela Tataiso ea Tlhokomelo le Ts'ebeliso ea Liphoofolo tsa Laborator (NationalResearchC Council, 1996).

Phekolo

Liphoofolo tsohle li kentsoe mofuta oa "cannulae" oa polasetiki ea 22g (Plastic One, Roanoke, VA) kahare ea morao-rao [rat: AP: 0.7, ML: -1.8, DV: -4.0 ∼ -5.0 (Paxinos le Watson, 1998); hamster: AP: + 1.0, ML, + 1.0, DV: -3.0 ∼ -5.0 (Morin le Wood, 2001), limilimithara ho tloha bregma], tlasa Na+ pentobarbital anesthesia (rat: 50 mg / kg, hamster: 100mg / kg) jwaloka ha ho hlalositsoe pele (Wood et al., 2004). Ts'ebetso tsohle tsa ts'ebetso ea opereishene li ne li etsoa tlas'a maemo a aseptic ho latela Melao-motheo ea Tlhokomelo ea liphoofolo (KE, 1985). Liphoofolo li ile tsa lumelloa ho fola bonyane beke e le 'ngoe ka mor'a ho buuoa pele ho hlahlojoa.

lithethefatsi

DHT, DHT-carboxymethyl-oxime (CMO), DHT-CMO-BSA, DHT-hemisuccinate (Hemis), le DHT-Hemis-BSA li fumanoe ho Steraloids (Newport, RI). Ho DHT-CMO-BSA, DHT e kopantsoe le BSA maemong a C3 le CMO e le sehokela. Ka mokhoa o ts'oanang, DHT e hokahane le BSA maemong a C17 ka Hemis ho theha DHT-Hemis-BSA. Ka bobeli DHT-CMO-BSA (Gatson et al., 2006) le DHT-Hemis-BSA (Braun le Thomas, 2003) li kile tsa sebelisoa ho etsa lipatlisiso tsa litlamorao tsa androgens ho membrane ea plasma. DHT e felisitsoe ka tharollo e nang le metsi ea 13% β-cyclodextrin (βCD, Sigma-Aldrich, St. Louis, MO) ho 1μg / μl. Joalokaha ho tsebahala ho tsoa thutong ea rona e fetileng ho li-hamsters, lethal dose lena le hlahisa ts'ebetso e matla ho arabela nakong ea tsamaiso ea ICV (DiMeo le Wood, 2006b). Lintho tse tlositsoeng ho DHT li qhibilihile ka koloing e le 'ngoe ka har'a khatello e lekanang ea DHT (DHT-CMO: 1.25 μg / μl, DHT-CMO-BSA: 8.7 μg / μl, DHT-Hemis: 1.34 μg / μl, DHT-Hemis-Bem : 8.83μg / μl). BSA (Sigma-Aldrich) e ile ea qhaloa ka koloing e le 'ngoe ho 7.45 μg / μl ho fihlela sephetho sa molora o lekanang oa BSA joalo ka DHT-CMO-BSA le DHT-Hemis-BSA. Lithethefatsi tse nang le BSA li ne li lokisoa letsatsi le letsatsi hang-hang pele ho sebelisoa ho qoba ho senyeha, 'me litharollo tsohle li ne li entsoe ka filthara ea 0.22 μm. Liphuputso tse fetileng li bontšitse hore ke karolo e nyane feela ea li-steroid tse tsoang BSA (Stevis et al., 1999), mme palo ena ha e na lekaneng ho fana ka litlamorao tsa bohlokoa tsa androgenic (Lieberherr le Grosse, 1994, Gatson et al., 2006). Ka mokhoa o ts'oanang, boithuto ba rona ba pejana bo bonts'itse hore DHT e itlhomme ho 1.0 μg / μl, empa eseng ho 0.1 μg / μl (DiMeo le Wood, 2006b). Kahoo, ho ke ke ha etsahala hore DHT ea mahala (> 10%) e ikarole ho BSA ka bongata bo lekaneng ho ts'ehetsa boipuso.

didirisiwa

Liphoofolo li ile tsa lumelloa ho itšebelisa tharollo ea lithethefatsi kapa koloi 4 hrs / letsatsi, matsatsi a 5 / beke ka phapusing ea basebetsi (Med Associates, St. Albans, VT) e kentsoe kamoreng e amohelang molumo ka moea o qobelloang. Kamore e 'ngoe le e' ngoe e ne e e-na le lesoba la ntlo, 2-nose pump, le pompo e laoloang ka k'homphieutha e hokeletsoeng moepeng oa metsi. Litharollo tse tsoang mosikong oa khalase tsa 100 μl li ile tsa tlisoa ho phoofolo ka ho kenella ka mothong oa Tygon o kopaneng le swivel. Leqhubu le hokahanyang swivel le cannula ea ICV e sirelelitsoe ke seliba sa tšepe. Tharollo ea lithethefatsi kapa koloi e ile ea tlisoa ka cannula ea kahare ea 28-ga e kentsoeng ka har'a cannula ea tataiso hanghang pele ho liteko. Infusion e 'ngoe le e' ngoe e ile ea tlisa 1 μl ea tharollo ho 0.2 μl / s. Ho na le masoba a Nose-poke a neng a le 6 cm ho tloha mokatong o ka tlase ho khanya ea ntlo. E 'ngoe ea masoba a hulang nko e ile ea khethoa e le sekoti se sebetsang sa nko. Karabo holima sekoti sena e tlalehiloe e le "nose-poke" e sebetsang (e matlafatsoang) mme e baliloe ho latela tlhoko ea karabelo (FR1 ho 5) bakeng sa ho baka ts'ebetso. Hang ha ts'oaetso e kentsoe, lebone la ntlo le ile la tima 'me lesoba le sebetsang le bonesitsoe nakong ea ts'ebetso ea 5-s ho thusa ho khetholla sekoti se sebetsang sa nko. Nose-poker ka sekoting se sebetsang nakong ena ea nako ea 5 e tlalehiloe empa ha ea ka ea bala mabapi le matlafatso (NR: e sebetsang-e sa matlafalitsoeng). Karabelo holima lesoba le leng la nko e ile ea tlalehoa e le "pua" e sa sebetseng empa ha ea ka ea baka ts'ebetso. Sebaka sa lesoba le sebetsang la nko ho ea ka pele kapa ka morao ho phaposi e ne e le taolo bakeng sa likhetho tsa lehlakore. Lintlha li tlalehiloe ke software ea WMPC (Med Associate) ho Windows PC.

Ts'ebetso ea ICV

Likhoto

Ho iketsetsa tsamaiso ea DHT ho litheko tsa Tfm le WT ho latela kemiso e nyolohang ea tekanyo (FR) ho tloha ho FR1 ho ea ho FR5. Likhoto li ne li koetliselitsoe pele ho FR1, moo karabelo e 'ngoe le e' ngoe e sebetsang ka nko e ileng ea matlafatsoa. Kamora moo, palo ea likarabo tse hlokahalang ho fumana infusion e ile ea phahamisoa ke e mong le e mong matsatsi a 5. Ho FR5, ho ile ha hlokahala likarabo tse hlano ho lesoba le sebetsang la nko bakeng sa infusion. Ka kakaretso, likhoto li ile tsa lekoa ho FR1 bakeng sa matsatsi a 10 le FR2 ho FR5 (matsatsi a 5 ka 'ngoe), ka matsatsi a 30 ka kakaretso. Likhoto tse tsoang mofuteng ka mong oa genotype li ne li abeloa lihlopha tsa DHT kapa koloi (Veh) ka tšohanyetso, 'me li lumelloa ho itaola DHT kapa koloi ea βCD, ka ho latellana. Liroto tse mashome a mararo a metso e tšeletseng (nWT = 19, nTfm = 17) li sebelisitsoe tekong ena.

hamsters

Hamsters e ile ea lekoa tlas'a kemiso ea FR1 bakeng sa matsatsi a 15. Lithutong tse fetileng, matsatsi a 15 a ho ipusa ka ICV T a lekane ho fumana khetho bakeng sa nko-poke e sebetsang. Hamsters e abetsoe ka mokhoa o sa sebetseng DHT (n = 8), DHT-CMO (n = 9), DHT-CMO-BSA (n = 10), DHT-Hemis (n = 11), DHT-Hemis-BSA (n = 8 ), kapa lihlopha tsa BSA (n = 9).

Tlhahlobo ea lintlha

Likhoto

Lipalo tsa likhetho tsa letsatsi le letsatsi bakeng sa nko e sebetsang ea nko li ne li khethoa ka ho tlosa mekotla e sa sebetseng ea nko ho tsoa kakaretso ea likoko tsa nko tse sebetsang le tse sa matlafalitsoeng (R + NR-I). Lenane la boikhethollo le bolelang hore phoofolo e 'ngoe le e' ngoe e khethiloe ho tloha matsatsing a 5 a ho qetela a FR1 le nakong ea FR2 ho ea ho FR5. Ntle le moo, lipalo tsa karolelano ea nako le nako bakeng sa phoofolo ka 'ngoe ho FR li ne li bapisoa.

Lintlha li ile tsa hlahlojoa ke 3-way ANOVA, e nang le genotype (WT kapa Tfm), lithethefatsi (DHT kapa koloi) le kemiso ea FR (1 ∼ 5) e le lintlha tse pakeng tsa taba. Kemiso ea FR e ile ea nkuoa e le karolo ea mantlha, hobane liphoofolo tse ling li ile tsa hloleha ho phethela matsatsi ohle a 30 a tlhahlobo ka lebaka la ho koaloa ha "cannula" ea tataiso ea ICV. Maemong ao, ke lintlha feela tse tsoang lithetlelelong tse tlatsitsoeng tse kenyellelitsoeng tlhahlobisong. Palo ea liphoofolo tse kenyellelitsoeng boemong bo bong le bo bong e bontšoa ho Lethathamo 1. ANOVA ea mekhoa e meraro e ile ea lateloa ke li-ANOVA tse loketseng ho latela melao e bonolo. Teko ea Newman-Keuls ea papiso ea bohlale ba post-hoc e sebelisitsoe ha ho hlokahala.

Lethathamo 1

Lethathamo 1

Boima ba 'mele (bolela ± SEM ho g) le palo ea likhoto tse sebelisitsoeng (n) qalong ea FR e' ngoe le qetellong ea FR5. * E fapane haholo le FR1 (p <0.05). # E fapane haholo le WT (p <0.05).

hamsters

Mokhoa o le mong oa R, NR, 'me ke ne ke sebelisetsoa tlhahlobo ea data. Palo ea khetho bakeng sa phoofolo ka 'ngoe e ne e khethiloe ka ho tlosa mokhoa o sa sebetseng oa nko-poke (I) ho tloha nko-poke (R + NR-I) e sebetsang. Ho ile ha hlahlojoa lintlha tse khetholloang pele ka tlhaiso e le 'ngoe t-Test khahlanong le 0 (ke hore, ha ho khethoe) bakeng sa sehlopha ka seng. Ntle le moo, palo ea likhothaletso tse fumanoeng e lekantsoe bakeng sa phoofolo ka ngoe. Matlafatso ea matla a fumaneng sehlopha ka seng sa lithethefatsi a ne a bapisoa le a taolo ea BSA ka sampole e ikemetseng ea 2 t-etona. Liphoofolo tse sa atlehang ho qeta boholo ba linako tsa 5 li ne li sa kenyelletsoe tlhahlobisong (1 e 'ngoe le e' ngoe ho tsoa lihlopheng tsa DHT-Hemis le DHT-Hemis-BSA).

Litlhahlobo tsohle tsa lipalo li ile tsa etsoa ho sebelisoa SPSS 12 (SPSS Inc., Chicago, IL). Bakeng sa tlhahlobo yohle, p <0.05 e ne e nkuoa e le ea bohlokoa. Lintlha li hlahisoa joalo ka ha li bolela ± SEM ka seboka sa 4h.

Results

WT le Tfm likhoto li ipusetse DHT

Oa araba

Lifeiga. 1 e bonts'a khetho e bolelang khetho e sebetsang ea nko (R + RN - I) ho FR ka 'ngoe bakeng sa lihlopha tsa DHT le Veh. Likhoto tse tsamaisang DHT li bontšitse khetho e kholo bakeng sa nko-poke e sebetsang (73.1 ± 7.6 resp / 4h), ha e bapisoa le taolo ea makoloi (29.8 ± 3.5 resp / 4h; F1,145 = 31.77, p <0.001). Hape ho bile le phello e kholo ea kemiso ea FR (F4,145 = 4.25, p <0.01), tšebelisano ea "genotype-drug" (F1,145 = 5.27, p = 0.02), le tšebelisano-leseling ea litla-morao tsa lithethefatsi (F4,145 = 2.60, p = 0.02). Ha ho na phello e ka sehloohong ea genotype, 'me litšebelisano tse ling li ne li se bohlokoa.

Setšoantšo sa 1

Setšoantšo sa 1

Iketsetse khetho (e sebetsang - e sa sebetseng ea nko-lipompo) bakeng sa likhoto tse itaolang DHT (holimo) le koloi (tlase). Ho bolela ± SEM ea FR e 'ngoe le e' ngoe e bontšoa, hammoho le kakaretso ea ± SEM (ka ho le letona). * E fapane haholo le FR1 (p < (Hape …)

Liteko tsa kamora ho hoc li senotse hore likhoto tse ikarolang DHT li bonts'a khetho e kholo ho feta kemiso ea FR (F4,73 = 4.18, p <0.01), ho eketsa khetho ho tloha ho FR1 (33.4 ± 4.4 resp / 4h) ho isa ho FR4 (110.8 ± 26.7 resp / 4h) le FR5 (106.4 ± 18.9 resp / 4h). Ha ho na phello ea genotype e bonoeng sehlopheng sena (kemiso ea genotype-FR: F4,73 = 0.13, ns; genotype: F1,73 = 0.86, ns).

Ho fapana le moo, likhoto tse ipehelang Veh ha lia ka tsa bontša phetoho ho feta kemiso ea FR (F4,72 = 0.31, ns), 'me ha ho na ts'ebelisano ea kemiso ea genotype-FR (F4,72 = 0.12, ns). Ho fapana le DHT, likhoto tsa Tfm li bonts'itse khetho e kholo ho feta WT sehlopheng sena (42.3 ± 5.3 le 19.1 ± 4.0 resps / 4h, ka ho latellana; F4,72 = 11.81, p <0.01).

Infusions

Palo e tloaelehileng ea infotainment ea DHT le Veh e fumanoeng ho FR e ngoe le e 'ngoe e bontšoa ho Feie. 2. Ka kakaretso, likhoto li fumane infusions e eketsehileng ha e lumelloa ho itaola DHT (26.9 ± 2.2 μg / 4h) vs. koloi (15.4 ± 1.9 μl / 4h, F1,145 = 14.70, p <0.001). Hape ho bile le phello e kholo ea kemiso ea FR (F1,145 = 3.32, p = 0.01), le tšebelisano ea lithethefatsi tsa genotype (F1,145 = 6.41, p = 0.01). Litšebelisano tse ling tsohle le litlamorao tse kholo li ne li se bohlokoa.

Setšoantšo sa 2

Setšoantšo sa 2

Ho bolela infusions e amoheloang ke likhoto tse ipehelang DHT (holimo) le koloi (tlase). Ho bolela ± SEM ea FR e 'ngoe le e' ngoe e bontšoa, hammoho le kakaretso ea ± SEM (ka ho le letona). * E fapane haholo le DHT FR1 (p <0.05). # Haholo (Hape …)

Karolelano ea karolelano ea letsatsi le letsatsi ea DHT likarolong tsohle tsa FR e ne e tšoana ho Tfm (24.3 ± 2.9 μg / 4hr) le WT (29.4 ± 3.4 μg / 4h) Ka lihlopha tsena ka bobeli, tšebeliso ea lithethefatsi e ile ea lula e le teng ha kemiso ea FR e ntse e eketseha (F4,73 = 0.54, ns). Nakong ea FR1, Tfm le banna ba WT ba ikarabellang ho DHT ho 24.5 ± 2.3 μg / 4h le 37.3 ± 6.7 μg / 4h, ka ho latellana. Tlas'a moralo oa FR5, tsamaiso ea boits'oaro ea DHT e kentse 18.3 ± 4.5 μg / 4h bakeng sa Tfm le 23.9 ± 5.9 μg / 4h bakeng sa likhoto tsa WT. Sehlopha sena ha sea ka sa bontša phapang e thehiloeng kemisong ea genotype- kapa genotype-FR (F1,73 = 1.17, ns; F4,73 = 0.34, ns, ka ho latellana).

Ka lehlakoreng le leng, litlalehong tsa Tfm le WT ka bobeli, palo ea infusions tsa koloi e theohile haholo ha tlhokahalo ea FR e ntse e eketseha (F4,72 = 4.73, p <0.01). Ho makatsang ke hore likhoto tsa Tfm li iketsetse koloi e batlang e imena habeli (20.7 ± 2.4 μl / 4h) joalo ka likhoto tsa WT (10.7 ± 1.4 μl / 4h, F1,72 = 7.77, p <0.01). Ho likhoto tsa Tfm ho FR1, palo ea li-infusions tsa koloi (39.9 ± 13.2 μl / 4h) e feta palo ea li-infusions tsa DHT (24.5 ± 2.3 μl / 4h). Leha ho le joalo, qetellong ea teko, tsamaiso ea boipheliso ea likoloi e ne e fokotsehile ho 10.3 ± 2.4 μl / 4h. Ka mokhoa o ts'oanang, likhoto tsa WT li iketselitse koloi ea 18.6 ± 4.1 μl / 4h ho FR1, e ileng ea hana ho 6.6 ± 1.8 μl / 4h ho FR5.

Boima ba 'mele bo bohlokoa qalong ea kemiso e' ngoe le e 'ngoe ea FR le palo ea liphoofolo boemong bo bong le bo bong bo bontšoa ho Lethathamo 1. Likhoto tsa WT li ne li le boima haholo ho feta likhoto tsa Tfm (F1,174 = 144.62, p <0.001), mme lihlopha tsohle li ile tsa nona kamora nako (F5,174 = 5.59, p <0.001). Ho ne ho se na phello ea boemo ba lithethefatsi (DHT vs Veh) ka boima ba 'mele (F1, 174 = 0.31, ns), kapa tšebelisano efe kapa efe. Ts'ebetso ea DHT e ntlafalitsoeng bakeng sa boima ba 'mele e ne e tšoana ho li-genotypes ka bobeli ho FR1 (WT: 77.9 μg / kg, Tfm: 65.4 μg / kg) le FR5 (WT: 46.5 μg / kg, Tfm: 42.6 μg / kg).

Li-hamsters tsa Syria li itlhomme DHT e kopantsoeng le BSA

Oa araba

Hamsters e ikemetseng DHT le DHT e kopaneng le BSA, empa eseng BSA feela. Setšoantšo sa 3a e bonts'a khetho e bolelang (e sebetsang-e sa sebetseng nko) bakeng sa DHT, BSA, DHT-CMO-BSA, le DHT-Hemis-BSA, DHT-CMO, DHT-Hemis. Tumellanong le lithuto tsa rona tsa pele, li-hamsters li ile tsa hlahisa khetho bakeng sa nko e sebetsang nakong ea ts'ebetso ea DHT (t7 = 4.34, p <0.01), empa a sa bontše khethollo ha a ithaopela BSA (t8 = 1.03, ns). Ka mokhoa o ts'oanang, li-hamsters li bonts'itse khetho bakeng sa nko e sebetsang ea nko ka bobeli DHT-CMO-BSA (t9 = 2.71, p = 0.02) le DHT-Hemis-BSA (t7 = 2.92, p = 0.02). E na le DHT e hokahantsoeng le lihokelo tsa eona feela, li-hamsters li ikentse DHT-CMO (t8 = 3.91, p <0.01), empa ha ea ka ea bontša khetho e kholo ha e ithaopela DHT-Hemis (t10 = 1.87, p = 0.09). Ka DHT-Hemis, likarabo ho nko e sebetsang (40.5 ± 10.3 resp / 4h) li ne li tšoana le tsa DHT-Hemis-BSA (41.2 ± 11.4 resp / 4h), empa banna bana ba bonts'a likarabo tse eketsehileng bakeng sa nko e sa sebetseng. -poke (28.7 ± 6.6 resp / 4h) bapisoa le ba DHT-Hemis-BSA (20.3 ± 4.4 resp / 4h).

Setšoantšo sa 3

Setšoantšo sa 3

3a: Ho bolela khetho (e sebetsang - e sa sebetseng ea nko) bakeng sa hamsters e itlhommeng BSA (n = 9), DHT (n = 8), DHT-CMO-BSA (DCB, n = 10) le DHT-Hemis-BSA ( DHB, n = 8), DHT-CMO (DC, n = 8), le DHT-hemis (DH, n = 11). * E fapana haholo le (Hape …)

Infusions

Palo ea infusions e fumanoeng bakeng sa sehlopha ka seng e bontšoa ho Feiga. 3b. Hamsters e amohetse DHT haholo ho feta BSA-infusions (t15 = 3.04, p = 0.01). Ka mokhoa o ts'oanang, hamsters e amohetse infusions e eketsehileng ha e lumelloa ho itaola DHT-Hemis-BSA (t15 = 2.72, p = 0.02) kapa DHT-CMO (t16 = 2.70, p = 0.02) bapisoa le BSA. Lipalo tsa infusions tse fumanoeng bakeng sa DHT-CMO-BSA (17.2 ± 3.2 μl / 4hr) le DHT-Hemis (22.7 ± 5.9 μl / 4hr) li ne li tšoana le lihlopha tse ikemetseng tsa DHT, DHT-Hemis-BSA, le DHT- CMO. Le ha ho le joalo, li-hamsters ha lia ka tsa amohela haholo DHT-CMO-BSA (t17 = 1.96, p = 0.07) kapa DHT-Hemis (t18 = 1.91, p = 0.07) bapisoa le BSA.

Ho overdose

Karolo e le 'ngoe ea li-hamsters tsa 55 li shoele pele li qeta lithuto tsohle tsa liteko tsa 15. Mafu a bolaeang ka lebaka la overdose ea androgen nakong ea tsamaiso ea testosterone a kile a hlalosoa pele (Peters le Wood, 2005). Thutong ea hona joale, 2 ea banna ba 8 (25%) ba hlokahetse nakong ea tsamaiso ea DHT, e ts'oanang le 24% e tlalehiloeng bakeng sa overdose ea testosterone (Peters le Wood, 2005). Ho iketsetsa tsamaiso ea DHT-CMO le DHT-Hemis ho ne ho amahanngoa le tahlehelo e phahameng ka ho fetisisa (3 e 'ngoe ea 8 ka sehlopha, 38%), ha ho ne ho e-na le likotsi tse fokolang pakeng tsa hamsters e ikemetseng BSA (1 ea 9, 11% kapa DHT -Hemis-BSA (0 ea 8). Joalo ka testosterone e sebelisitsoeng ho feta tekano, ha ho le ea mong oa hamsters thutong ea hona joale ea ileng a hlokahala nakong ea boitaolo. Ho fapana le moo, hamsters o ile a hlokahala lihora tse 'maloa hamorao a le mekotla ea bona ea lapeng, a na le matšoao a tebileng a ho sithabela maikutlo le khatello ea maikutlo.

Testosterone overdose e hokahane haholo le tšebeliso ea testosterone, haholo-holo boholo ba ho ja ka nako e le ngoe (Peters le Wood, 2005). Feie. 4 e bapisa lintlha tse khethiloeng, palo ea likhothaletso tse fumanoeng, le tlhalo e phahameng ea li hamsters tse qetileng lithuto tsohle tsa liteko tsa 15, le ba sa kang ba etsa joalo. Lihlopheng ka bobeli li bontšitse khetho e matla bakeng sa nko e sebetsang (Nko-poke)p <0.05). Leha ho le joalo, khetho e ne e le kholo haholo ho li-hamsters tse shoeleng nakong ea boipuso (25.7 ± 5.2 resp / 4h) ha li bapisoa le tse ileng tsa phela (9.5 ± 2.0 resp / 4h, t53 = 3.42, p <0.01). Hamsters e hlōlehileng ho phethela mananeo a 15 e amohetse li-infusions tse fetang habeli ka nako (31.2 ± 5.0 inf / 4h) joalo ka ba phethileng mananeo ohle (14.8 ± 1.1 inf / 4h, t53 = 5.05, p <0.001). Ntle le moo, bakeng sa li-hamster tse shoeleng nakong ea thuto, palo e phahameng ea batho ba kenang ka nako e le ngoe e ne e phahame haholo (77.0 ± 9.8 inf / 4h) ho feta ea banna ba ileng ba phela (36.1 ± 2.9 inf / 4h, t53 = 5.41, p <0.001).

Setšoantšo sa 4

Setšoantšo sa 4

Ho boleloa likhetho tse khethiloeng (ka ho le letšehali), li-infusions tse amoheloang (bohareng), le palo e phahameng ea batho ba kenang ka nako e le ngoe (ka ho le letona) bakeng sa li-hamsters tse phethileng mananeo ohle a 15 (C15, n = 44) le ba sa kang ba (<15, n = 11). Sehlopha se bolela ± SEM li bonts'oa e le moriri o sefapano. (Hape …)

Puisano

Ts'ebetso ea boithatelo ba Androgen e kanna ea kopanngoa le li-membrane tse amanang le tsona, empa eseng ka li-receptor tsa nyutlelie le androgen

Boithuto ba hona joale bo bonts'a hore li-AR tsa khale tsa nyutlelie ha li bohlokoa bakeng sa ho itaola le androgen. Ka bobeli likhoto tsa Tfm le WT li hlahisitse khetho bakeng sa pompong e sebetsang ea nko nakong ea taolo ea DHT. Ntle le moo, ba ile ba khona ho arabela lenaneong le nyolohang la 'maraka ka ho eketsa marang-rang a nko, ka ho etsa joalo ba boloka tekanyo e tsitsitseng ea ho sebelisa lithethefatsi ho sa natsoe kemiso ea FR. Ho fapana le moo, likhoto tse amohelang likoloi li ile tsa sitoa ho araba liphetoho tsa kemiso ea FR. Li-poker tsa bona tse sebetsang ha lia ka tsa eketseha haholo ho arabeleng liphetoho kemisong ea FR, 'me ba amohetse infusions tse fokolang ha tlhoko ea karabelo e ntse e eketseha. Hobane ligand e tlamang "li-androgen receptor" ea "khale" e kenelletse liphatlalatsong tsa Tfm, sena se ts'ehetsa maikutlo a rona a hore ntlafatso ea androgen e kopantsoe ka litsela tse ling.

Karabelo e phahameng e sa lebelloang bakeng sa koloi ka likhoto tsa Tfm ha e na monyetla oa ho ba ka lebaka la koloi ka boeona. Re bone liketsahalo tse tšoanang sehlopheng se arohaneng sa likhoto tsa Tfm tse neng li sa fumane infusions (data e sa bontsitsoeng). Sebakeng seo, e kanna ea amana le litšobotsi tsa boits'oaro ba basali ho banna ba Tfm. Meno a eketsehang a nko a litoeba tsa Tfm e kanna ea ba a khahlapetsa ho li-dips tsa hlooho tse phahameng tse bonoang ho likhoto tsa basali (Brown le Nemes, 2008). Ntle le moo, likhoto le litoeba tsa Tfm li tsejoa li bontša boits'oaro bo ts'oanang le boits'oaro bo joalo (Zuloaga et al., 2006, Zuloaga et al., 2008a). Mohlomong, litla-morao tsa khatello ea kelello tsa DHT (Agren et al., 1999, Arnedo et al., 2000, Frye le Seliga, 2001, Berbos et al., 2002, Peters le Wood, 2005) e hlakisitse boitšoaro bo kang ba ho tšoenyeha ha Tfm e itheola DHT.

Ntle le moo, boits'ebetso ba li-conjugates tsa DHT-BSA ka li-hamsters tsa banna ho fana ka bopaki ba hore androgens e ka sebetsa ho membrane ea plasma ea neuronal ho ba le ts'ebetso e matlafatsang. Hamsters e bontšitse khetho e kholo bakeng sa li-conjugates tsa DHT-BSA ka bobeli. Litekanyetso li ipapisitse le lithuto tsa rona tse fetileng ho T, DHT, le li -idsids tse atisang ho hlekefetsoa (Ballard le Wood, 2005, DiMeo le Wood, 2006b). Ka lehlakoreng le leng, li-hamsters ha li bontše ho rata BSA feela. Lintlha tse mabapi le lefu la motho le tšebeliso ea lithethefatsi li bonts'a DHT le lihlahisoa tsa eona li ka ba kotsi, tsa ho phahamisa data ea rona ea pele ho T overdose (Peters le Wood, 2005).

Phuputso ea morao-rao e senola mofuta o ikhethang oa ts'ebetso ea karabo. Hamsters ha a ka a khetha mokokotlo o sebetsang oa nko ha o ntse o ikoetlisa, joalo ka ha ho bonts'itsoe pejana (Johnson le Wood, 2001, Wood, 2002, DiMeo le Wood, 2004, Triemstra le Wood, 2004, Wood et al., 2004, Ballard le Wood, 2005, DiMeo le Wood, 2006b). Literateng, leha ho le joalo, ho ne ho e-na le khetho e hlakileng bakeng sa ho kuta-nko ho mafolofolo ho sa tsotelehe sehlahisoa se amoheloang. Re hlokometse mokhoa o tšoanang thutong ea rona ea pejana mabapi le ho itaola ha T ka likhoto, leha e ne e se ntho ea bohlokoa ka lipalo (Wood et al., 2004). Ho ipapisitsoe le phapang e ikhethileng ea boits'oaro bo itlhommeng pele, ho tlameha ho nkuoe tlhokomeliso ha ho bapisoa data ea boits'oaro ho litoeba le li-hamsters.

Hona le likheko tse 'maloa tse hlokang ho hlahlojoa ha ho hlalosoa thuto ea hona joale. Taba ea mantlha, li-AR tsa nyutlelie tse nang le botsitso bo boholo ba ligand li ntse li le teng liphatseng tsa Tfm (Yarbrough et al., 1990), ho fapana le litoeba tsa Tfm (He et al., 1991). Ho ka etsahala hore li-ars tsena tsa nyutlelie tse fetotsoeng li lekane bakeng sa lipakeng tsa litlamorao tsa androgens litekong tse kholo tsa 'mele. Taba ea bobeli, li-conjugates tsa DHT-BSA li ka fokola Ka vivo, e hlahisang DHT ea mahala. Leha sena se sa bonahale e le bothata ba bohlokoa a vitro (Lieberherr le Grosse, 1994, Gatson et al., 2006), tekanyo le nako ea tlholeho ea DHT-BSA Ka vivo bokong hajoale ha ho tsejoe. Kamora nako, li-conjugates tsa DHT-BSA li ka 'na tsa se ke tsa kenella haholo bokong ba boko. DHT-BSA e kholo haholo ho feta DHT, ka hona litlamorao tsa DHT-BSA tse bonoang thutong ea hajoale li kanna tsa kopanngoa libakeng tse haufi le li-ventricles.

Leha ho na le likatse tsena, mekhoa ena e 'meli e fapaneng e hlahisitse liphetho tse lumellanang tse matla khahlanong le tlhokahalo ea matla a nyutlelie ka har'a ts'ebetso ea androgen. Ntle le moo, boits'oaro ba li-conjugates tsa BSA bo fana ka maikutlo a hore androgens e ka sebetsa ho membrane ea plasma ho matlafatso ea androgen. Ho tsebo ea rona, thuto ea hona joale e fana ka ea pele Ka vivo bopaki ba litlamorao tse mabapi le boits'oaro bo botle ba androgens ho membrane ea plasma.

Androgens e fana ka litlamorao tse potlakileng tsa boipuso tsa AR tsa nyutlelie moputsong

Lithuto tse ling tse 'maloa mabapi le moputso oa androgen li bonts'itse liphetho tse lumellanang le litlamorao tse seng tsa genomic kapa tsa plasma. CPP e nts'etsapele ka hare ho 30 min ea sindic T ea systemic (Alexander et al., 1994), thupelo ea nako e tsamaisanang le litlamorao tse mpe tse seng tsa genomic tsa T. CPP le tsona li ka susumetsoa ka infusions ea Acb ea T kapa metabolite (Packard et al., 1997, Frye et al., 2002), leha Acb e na le lipalo tse fokolang tsa genomic AR. Ntle le moo, VTA e bontša Fos ha a arabela ts'ebetsong ea ICV T-infusion (Dimeo le Wood, 2006a), leha ho na le khaello e kholo ea polelo ea khale ea AR moo. Boithuto ba hajoale ha bo fane ka leseli mabapi le sebaka sa ts'ebetso bokong. Le ha ho le joalo, e bontša hore khaello e lekanyelitsoeng ea nyutlelie ea AR feela ha se lebaka le lekaneng la ho qhelela ka thoko meaho e kang Acb le VTA libakeng tse ka bang teng lipakeng tsa litla-morao tsa androgenic.

Litlamorao tse potlakileng tsa lera la plasma tsa li-steroid ho dorsal le ventral striatum ha li felle ho li-androgens. Li-progestin li tsejoa ho hohela CPP, mohlomong ka li-receptor tsa gamma-aminobutyric acid (GABA) ho Acb (Frye, 2007). Estrogens e boetse e fana ka litlamorao tse potlakileng, tsa membrane receptor-Mediated ho dorsal striatum (Mermelstein et al., 1996, Becker le Rudick, 1999). Receptor e amanang le membrane e se e arotsoe bakeng sa li-progestin (Zhu et al., 2003), mme bopaki bo bokellana bakeng sa li-receptor tsa cell-holim'a li-estrogens (tse lekiloeng ho Vasudevan le Pfaff, 2007) le androgens (e lekantsoe ka Thomas et al., 2006). Ha li-estrogener hape li matlafatsa (DiMeo le Wood, 2006b), litlamorao tse matlafatsang tsa T li bonahala e le tsa androgenic haholo. Hamsters e itlhommeng le ho se sebetse ka li-androgens tse sa kopaneng, joalo ka drostanolone le DHT (Ballard le Wood, 2005, DiMeo le Wood, 2006b). Ntle le moo, anti-androgen flutamide e ka thibela T-tsamaiso ea (Peters le Wood, 2004). Le ha hona ho ka bonahala ho hanana le karolo ea membrane AR e tlalehiloeng thutong ena, ho tlalehiloe hore Flutamide e thibela activation ea membrane le (Braun le Thomas, 2003, Braun le Thomas, 2004).

Melemo ea li-receptor tsa androgen le membrane

Ntle le nalane, litlamorao tsa li-steroid, ho kenyelletsa le li-androgens, li ne li nkuoa li fetisoa ke lits'ebetso tsa methapo ea nyutlelie. Leha ho le joalo, litlaleho tsa litlamorao tse potlakileng tsa androgen, tseo mohlomong li kopantsoeng le li-receptor tse amanang le membrane, li se li le teng ka mashome a lilemo a 'maloa. Mohlala, sebakeng sa medial preoptic, androgens e ka fetola ho thunya ha neuronal nakong ea metsotsoana e seng mekae (Yamada, 1979) ho isa metsotso (Pfaff le Pfaffmann, 1969). Ho feta moo, Orsini le basebetsi-mmoho (Orsini, 1985, Orsini et al., 1985) e bontšitse phetoho e potlakileng ea khafetsa ea ho thunya ha neuronal ka li-androgens ho "lateroth hypothalamus" (LHA). Kameho ena ea li-androgens ho LHA ​​e kanna ea ameha haholo ho thuto ea hona joale, kaha LHA e tsejoa ho nka karolo mokhatlong oa moputso (Ba baholo le Milner, 1954) le LHA orexin / hypocretin e laoloa ke gonadal steroids (Muschamp et al., 2007).

Mefuta ea lisele tse nang le li-membrane tse nang le bokhoni ba kenyeletsa glial (Gatson et al., 2006), gonadal (Braun le Thomas, 2003, Braun le Thomas, 2004)Benten et al., 1999, Guo et al., 2002), myocyte (Estrada et al., 2003), le li-osteoblasts (Lieberherr le Grosse, 1994). Le ha boitsebiso ba molek'hule bo ntse bo tlameha ho tsejoa, bakuli ba membrane AR ba kenyelletsa li-membrane receptor le libaka tse tsejoang tsa binding tsa steroid, joalo ka GABA-A (e hlahlobuoe ho Lambert et al., 2003) le li-subrits tsa NR2 tsa li-receptor tsa N-methyl-D-aspartic acid (Malayev et al., 2002). Ntle le moo, Thomas le basebetsi-mmoho (2004) ba tlalehetse bopaki bakeng sa palesa ea G-protein e kopantsoeng e le membrane AR. Ntle le moo, litlamorao tsa androgens tse sa amaneng le receptor e itseng li ka se kenyelletsoe thutong ea hona joale.

Recent a vitro lithuto li fana ka maikutlo a hore ho na le li-membrane tse ngata tsa membrane, kapa sebaka se fetang se le seng se tlamang ho receptor e le 'ngoe, joalo ka ha ho reriloe ho receptor ea membrane progesterone (Ramirez et al., 1996). Mefuteng e mengata ea lisele, membrane AR e bonahala e le setsi sa membrane se kopantsoeng le Gq / o (Lieberherr le Grosse, 1994, Benten et al., 1999, Zhu et al., 1999, Guo et al., 2002, Estrada et al., 2003). Leha ho le joalo, litšobotsi tse tlamang tsa steroid le kutloisiso ea maikutlo ho anti-androgens ea membrane ea membrane ea AR li fapana haholo ho latela mofuta oa sele. Mohlala, li-anti-androgens li ka thibela litlamorao tsa DHT liseleng tsa "oache" tsa "croaker"Braun le Thomas, 2003, Braun le Thomas, 2004), leha li sa sebetse ka mefuta e meng ea lisele (Lieberherr le Grosse, 1994, Benten et al., 2004, Gatson et al., 2006), kapa e ka hlahisa litlamorao tse kang tsa agonist liseleng tsa hippocampal (Pike, 2001, Nguyen et al., 2007) le mela e 'maloa ea sele ea mofets'e (Peterziel et al., 1999, Zhu et al., 1999, Evangelou et al., 2000, Papakonstanti et al., 2003). Ntle le moo, ho tlalehiloe likarolo tse fapaneng tsa ho tlama ha litho tse fapaneng tsa lihlapi (Braun le Thomas, 2004).

Phihlelo ea rona ea AAS e hlekefetsoang hangata e bonts'a hore liphetoho tse kholo ho A-ring (ho C2 le / kapa C3) le C17 li tloaetse ho kena-kenana le boits'ebetso (Ballard le Wood, 2005). Mohlala, stanozolol, e nang le phetoho e kholo ho C2 le C3 hammoho le sehlopha sa methyl se khomaretsoeng C17, ha e laolehe. Thutong ea morao-rao, hamsters e itlhomme ka bobeli BSA e kopane ho C3 (DHT-CMO-BSA) le C17 (DHT-Hemis-BSA). Ho hlokahala patlisiso e eketsehileng ho hlakisa litšobotsi tsa androgens eo e itlhommeng pele.

Bohlokoa ba tleliniki

AAS, haholo-holo T, ke batšehetsi ba bangata ba ntlafatsang ts'ebetso ba sebelisoang ke baatlelete, ba ikarabellang bakeng sa halofo ea liteko tse hlakileng tsa phallo (Mokhatlo oa Lefatše o Khahlano le Doping, 2006). Ka lebaka la ts'ebeliso e pharalletseng joalo, tlhekefetso ea AAS e na le litlamorao tse fapaneng tsa bophelo bo botle. Litla-morao tsa pelo le litla-morao tsa ho hlekefetsoa ha AAS li thehiloe hantle (Leshner, 2000). Tsena le litlamorao tsa anabolic tsa AAS li 'nile tsa nahanoa hore li ka hokahanngoa ka matla a nyutlelie a AR. Leha ho le joalo, litlamorao tse ka bang teng tsa nyutlelie-e ikemetseng ea li-androgens li bontša hore tšusumetso ea AAS e kanna ea atoloha ho feta meaho ka polelo ea nyutlelie ea AR.

Ha ho bapisoa le lithethefatsi tse ling tsa tlhekefetso, AAS e hlahisa litlamorao tse fapaneng mme e na le mekhoa e fapaneng ea ts'ebetso ho tsoa ho li-stimulants. Ho fapana le li-stimulants (Graybiel et al., 1990), AAS e kenya ts'ebetsong ea c-Fos feela ho VTA eseng ho Acb (Dimeo le Wood, 2006a). Ntle le moo, AAS e fana ka tlhahiso e matlafatsang e susumetsang ea Acb DA e ntšitsoeng (Birgner et al., 2006), le ho thibela hore DA e lokolloe (Triemstra et al., 2008). Boitšoaro, AAS ha e khothalletse ts'ebetso ea ts'ebetso ea locomotorPeters le Wood, 2005).

Ho fapana le moo, likarabo tsa boits'oaro ho AAS e hlobaetsang li tšoana le tsa li-opioid kapa li-benzodiazepines, mohlomong li fana ka litlamorao ha li kopane. Ho pepeseha ka matla ho AAS ho nyenyefatsa mesebetsi ea boits'ireletso, ho kenyelletsa ho hema le mocheso oa mmele (Peters le Wood, 2005). Ho sithabela ha maikutlo a tlhasimolloang ke AAS ho hopotsa matšoao a opioid ea ho fetella, mme e thibetsoe ke opioid antagonist naltrexone (Peters le Wood, 2005). Ho feta moo, nandrolone, AAS e sebelisoang hangata, e na le litlamorao tsa hypothermic tsa morphine le exacerbate naloxone-precipended morphine dalili tsa ho tlohela (Celerier et al., 2003). Ntle le moo, ho thehiloe ka nepo hore AAS e hlobaetsang ea ho susumetsaAgren et al., 1999, Arnedo et al., 2000, Frye le Seliga, 2001, Berbos et al., 2002, Peters le Wood, 2005), mohlomong e kopantsoeng le litlamorao tsa tsona tse tobileng ho GABA-A receptors (Masonis le McCarthy, 1995, Masonis le McCarthy, 1996). Ho eketsa ts'ebeliso ea ethanol ho likhoto tse tšoaroang hampe ke AAS le eona e ka ba sesupo sa mosebetsi o fetotsoeng oa GABAergic (Johansson et al., 2000).

Seo re se fumaneng ho overdose se hlahisa kameho e eketsehileng ea bophelo bo botle. Hajoale, sehlopha sa AAS e le lintho tse laoloang se ipapisitse le thepa ea tsona ea anabolic (Molao oa Lintho tse Laoloang, 1991). Leha ho le joalo, thuto ea hona joale e bonts'a hore katleho ea anabolic ea AAS ha e hlile ha e tsamaisane le thepa ea bona ea ho matlafatsa le likotsi tsa ho fetelletsa. Ntle le li-conjugates tsa DHT-BSA, DHT-CMO e sebelisitsoeng thutong ena ha se ntho e laoloang, leha thepa ea eona e matlafatsang le lefu ho tsoa ho litekanyetso tsa eona tse ngata li bonahala li ts'oana le DHT le T (Peters le Wood, 2005). Mokhoa oa overdose o boetse o tšoana le o neng o tlalehiloe T ka nako eo (Peters le Wood, 2005), moo ho nona ho phahameng ho ileng ha fella ka lefu la 24 ho 48 hrs hamorao. Ka lebaka la liphumano tsena, mekhoa e sebelisitsoeng bakeng sa ho hlophisa steroid e le ntho e laoloang e ka hloka hore ho hlahlojoe boikarabello bakeng sa tlhekefetso ea eona ea tlhekefetso le tahi, ntle le tumello ea eona ea anabolic.

Liphetho tsa boithuto ba hona joale li bontša hore AR ea nyutlelie, e le eona feela AR e ikemetseng ho fihlela joale, ha e bohlokoa bakeng sa matlafatso ea androgen. Sebakeng seo, liphetho li fana ka maikutlo a hore ntlafatso ea androgen e fetisoa ho membrane ea plasma. Ka hona, lipatlisiso tse eketsehileng mabapi le boitsebiso ba sebopeho sa membrane ea putative, litšobotsi tsa bona tsa ts'ebetso le kabo ea anatomical li hlokahala ho hlakisa moelelo oa ts'ebeliso e mpe ea AAS le litlamorao tsa eona tsa bongaka.

Mongolo o botlaaseng ba leqephe

Boitlhotlhollo ba Mohoeletsi: Ena ke faele ea PDF ea mongolo o ngotsoeng ka letsoho o sa amoheloang o amoheletsoeng bakeng sa ho hatisoa. Joaloka tšebeletso ho bareki ba rona re fana ka phetolelo ena ea pele ea mongolo o ngotsoeng ka letsoho. Mongolo o ngotsoeng ka letsoho o tla ba le ho kopitsa, ho kenya lihlopha le ho hlahloba bopaki bo hlahang pele o hatisoa ka mokhoa oa oona oa ho qetela. Ka kopo hlokomela hore nakong ea mekhoa ea tlhahiso ea lihlahisoa e ka fumanoa e ka amang litaba, le litsebiso tsohle tsa molao tse sebetsang koranteng e amanang le eona.

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