Bacha le Androgens, Bafani le Meputso (2008)

inahaneloang

Overview

Nako ea bocha e tsosetsa kelello molemong oa ho ithabisa le ho ipeha kotsing. Bacha ba batho, hangata sena e ba mofuta oa teko ea lithethefatsi le thobalano. United States, nako ea bohareng ea ho etsa thobalano ho ba batona ke lilemo tse 16.4, 'me 65% e bile le thobalano ka sehlopha sa 12th (Kaiser Family Foundation, 2005). Ka mokhoa o ts'oanang, sechaba sena se na le litheko tse phahameng haholo tsa lithethefatsi tse seng molaong United States. Ho latela lipatlisiso tsa naha tsa 2004 mabapi le tšebeliso ea lithethefatsi le bophelo bo botle, 38% ea banna ba lilemo tsa 18-25 o sebelisitse sethethefatsi se seng molaong selemong se fetileng (SAMHSA / OAS, 2005). Ho feta moo, 31% ea bashemane ba bacha ba ile ba sebelisa lithethefatsi kapa joala nakong ea ha ba ne ba kopana ka nako ea ho etsa thobalano.Kaiser Family Foundation, 2005). Ntle le moo, nako ea bocha ke nako ea bohlokoahali ho etiology ea psychopathologies e itseng, joalo ka khatello ea maikutlo, ho tšoenyeha, ho ja ho se nang tumelo le bokuli ba boitšoaro. Re ikemiselitse hore secretion ea pubertal ea li-hormone tsa gonadal, ts'ebetso ea tsona ea li-receptor tsa steroid bokong, le tšebelisano lipakeng tsa li-hormone le boiphihlelo holima bongoaneng ba bongoana bo kenya letsoho phetohong ea boitšoaro e bonoang nakong ea bocha.

Morero oa rona mona ke ho hlahloba bopaki ba hore gonadal androgens e hokahanya bocha ba bocha le ts'ebetso ea batho ba baholo ea boits'oaro bo khothalletsoang, hammoho le thepa e ntle ea boitšoaro bona. Re fana ka bopaki ba hore testosterone ka boeona ea putsa, e ka 'nang ea tlatsetsa phetohong e kholo ea boits'oaro bo susumetsoang nakong ea bocha, ha maemo a testosterone a phahama. Tsepamiso ea pampiri ena e lithutong tsa rona tsa li-circuits tsa neural tse ka tlase tsa boitšoaro ba banna ba botona le botšehali, haholo-holo ho sesole sa Syria, ka ho totobatsa ho sebelisana pakeng tsa testosterone le dopamine (DA). Re fana ka maikutlo a hore li-androjeni tsa "pubertal androgens" li na le litlamorao tsa nako e telele le tsa nako e telele ho li-circuits tsa meputso le boitšoaro bo khothalletsoang. Re boetse re phahamisa hore tlatsetso le li-androgens tsa kantle tsa mofuta oa li-anabolic-androgenic steroids (AAS) li eketsa tšusumetso e tloaelehileng ea li-pubertal androgens, ka hona li ama hampe tsoelo-pele ea bongoana le boits'oaro.

Nako ea bocha ke nako e mahlonoko bakeng sa kholo ea boko

Qetellong, boko ke sesosa le sepheo sa ketso ea androgen nakong ea bocha. Ho bashanyana ba banyenyane (<lilemo tse 12) le li-hamsters tse nyane (<matsatsi a lilemo tse 28), li-androgens le li-gonadotropin tse potolohang li maemong a tlase. Ha sephiri sa luteinizing hormone e tsoang pōpelong ea anterior pituitary e phahama ka lebaka la hypothalamic gonadotropin-release hormone, ho potoloha hoa testosterone ho eketseha haholo. Sena se etsahala ka sethaleng sa Tanner II / III (lilemo tse 14) ho bashanyana, le ka matsatsi a 28 a li-hamsters. Nakong eo bashanyana ba fihlang sethaleng sa Tanner IV / V (lilemo tse ka bang 16) kapa ha li-hamsters li le matsatsi a 50-60, testosterone ea ho qetela e se e le hara banna ba baholo. Sephiri sa "pubertal hormone" se tsamaellana le nako ea bocha, e etsahalang ho tloha lilemong tse 12 ho isa ho tse 20 ho batho. Lihormone tsa bongoaneng ha li sebetse feela lithong tsa 'mele ho baka ponahalo ea litšoaneleho tsa thobalano tsa bobeli tseo e leng matšoao a totobetseng a ho kena bohlankaneng, empa hape li sebetsa bohareng ho susumetsa ntlafatso ea boko ba bocha le kholo ea boitšoaro. Ntle le moo, liphetoho tsa "physiologic" le "neurologic" tse tlisoang ke "hormone" ea "pubertal" li lebisa liphetohong tse kholo phihlelong ea motho, e leng eona e ka fetolang kholo ea kholo ea boko. Kahoo, keketseho ea bokhachane ba lihormone tsa thobalano tsa steroid, e tsamaisoang ke kholo ea nako e holang ea ho tsoala ea neuroendocrine axis, ka lehlakoreng le leng e theha nts'etsopele ea boits'oaro ba bocha ka litšusumetso tse tobileng le tse sa tobang tsamaisong ea methapo.

Bocha ba motho joale bo amoheloa e le nako e kholo le e matla ea nts'etsopele ea neural nakong eo lipapatso tsa boits'oaro li ntlafatsoang le ho ntlafatsoa. Le ha boko ba ngoana ea lilemo li 5 e se e le 90% ea boholo ba eona e kholo (Dekaban, 1978), ho nchafatsoa hoa bohlokoa ho sa ntse ho tla. Mohopolo ona o ile oa khothaletsoa ke lipatlisiso ho batho le liphoofolo tse tlalehang hore mekhoa e mengata ea nts'etsopele ea mantlha e etsahalang nakong ea kholo ea kelello ea bongoana e phetoa hape nakong ea bohlankana. Ts'ebetso tsena li kenyelletsa neurogeneis (Eckenhoff le Rakic, 1988; Eena le Crews, 2007; Pinos, Collado, Rodriguez-Zafra, Rodriguez, Segovia, le Guillamon, 2001; Rankin, Partlow, McCurdy, Giles, le Fisher, 2003),Nunez, Lauschke, le Juraska, 2001; Nunez, Sodhi, le Juraska, 2002), ho hlakisoa le ho hlatsoa ha li-dendritic arborizations le li-synapses (Andersen, Rutstein, Benzo, Hostetter, le Teicher, 1997; Huttenlocher le Dabholkar, 1997; Lenroot le Giedd, 2006; Sowell, Thompson, Leonard, Welcome, Kan, le Toga, 2004), myelination (Benes, Turtle, Khan, le Farol, 1994; Paus, Collins, Evans, Leonard, Pike, le Zijdenbos, 2001; Sowell, Thompson, Tessner, le Toga, 2001), le phapang ea thobalano (Chung, De Vries, le Swaab, 2002; Davis, Shryne, le Gorski, 1996; Nunez et al., 2001). Kahoo, tšubuhlellano ea bongoana ea kamora 'matsatsi a pelehi ha e tsamaisane, empa ho e-na le hoo e khetholloa ke ho phatloha ho hoholo hoa bongoana' me ho kenyelletsa liketsahalo tse tsoelang pele le tse khahlisang. Joalokaha setsebi leha e le sefe sa kholo ea tsoelo-pele se tseba, linako tsa liphetoho tse potlakileng tsa ntlafatso li ile tsa phahamisa kutloisiso le ho ba kotsing ea phetoho e itšetlehileng ka boiphihlelo le litlamorao tse mpe tsa ho nyelisoa le ho rohakoa, 'me ha ho na lebaka la ho nahana hore kholo ea bongoana ea bongoana e sa le letho.Andersen, 2003; Spear, 2000). Kahoo, litlatsetso nakong ea tšusumetso ea li-hormone tsa "pubertal" bokong ba bongoana li ka boleloa esale pele hore li tla ba le litlamorao tsa nako e telele bakeng sa boitšoaro ba motho e moholo.

Androgens le Li-Circuit tsa Neural bakeng sa Boitšoaro bo Khothatsang

Hobane nako ea bocha ke karolo ea nakoana le e matla ea ntlafatso, ho ka ba thata ho lekola kelello le boits'oaro ba mocha ka bo mong. Sebakeng seo, ho ananela botho bo ikhethang ba bocha, ho molemo ho bo bapisa le kelello le boits'oaro ba batho ba baholo ba holileng tsebong. Kahoo, ka ho shebisisa leqephe lena mabapi le boitšoaro ba monna le thobalano ea banna, ho bohlokoa mona ho hlahisa li-circuits tsa neural bakeng sa ho qopitsa le takatso ea thobalano ho banna ba baholo, ho kenyelletsa karolo ea li-hormone tsa gonadal tsa ts'ebetso ea ts'ebetso ea ts'ebetso le phetiso ea li-receptor bakeng sa androgens (AR) le estrogens (ER).

AR e teng ka lihlopha tsa lisele tse bopa mekoloko ea neural e tsamaisang mekhoa e metle ea boits'oaro sechabeng, joalo ka thobalano. Ntle le moo, boko ba mofuta oa bongoana bo hlahisoa pele ho nako ea ho kena bohlankaneng kapa boroetsana mme ba khothatsoa ke li-androgen ho banna le bana ba baholo (Kashon, Hayes, Shek, le Sisk, 1995; Meek, Romeo, Novak, le Sisk, 1997). Boko ba methapo, ho na le phapano e kholo ho abeloeng ha AR le ER (Wood le Newman, 1995), le aromatase (Celotti, Negri-Cesi, le Poletti, 1997), ho kenyelletsa mefuta ea α le β ea estrogen receptor (Shughrue, Lane, le Merchenthaler, 1997). Ha e tlama ligand, "classical" AR le ER li sebetsa e le mabaka a ho qobella ho ngola le ho hlophisa liprotheine tse ncha. Ha ho makatse hore ebe litla-morao tsena li latela nako butle-butle, ka ho lieha ho nka bohato. Ho ts'oaroa ha Steroid ea boits'oaro ba monna HamsterNoble le Alsum, 1975) e lumellana le liketso ka liketso tsa khale tsa genomic. Mohlala, libeke tsa 2 tsa ho pepesetsoa ha steroid ho hlokahala ho khutlisetsa mathe ka li-castrate tsa nako e telele. Phuputso ea morao-rao ea litoeba e boetse e bonts'a litla-morao tsa kapele tsa li-androgens libakeng tsa boko tse nang le li-receptor tse fokolang tsa classical (Mermelstein, Becker, le Surmeier, 1996). Ts'ebetso tsena tsa steroid ho nahanoa hore li kenella ka li-receptors tse seng tsa genomic. Athe ho ajoa ha classical AR le ER bokong ba hamster ho lekantsoe (Wood le Swann, 1999), litebello tse ka bang teng tsa boko bakeng sa ts'ebetso eo eseng ea genomic androgen li ngata haholo.

Sebaka sa medial preoptic (MPOA) se bapala karolo ea mantlha ea ho kopitsa ho banna ho tloha ho lihlapi tsa khauta ho ea ho batho (e lekantsoe ho Hull, Wood le McKenna, 2006). Ho feta moo, Hamster MPOA e fetisetsa lihormone tsa gonadal steroid ka bongata ba AR le ER, le li-implants tsa testosterone ho MPOA li lekane ho khutlisa ts'ebetso ea thobalano ho li-castrate tsa nako e telele (Wood le Swann, 1999). Likotong tsa banna, gonadal steroids e sebetsa ho MPOA ho laola ho lokolloa ha DA ho basal (Putnam, Sato, le Hull, 2003) le ho susumetsa ho ruruha (Hull, Du, Lorrain, le Matuszewich, 1995). Pele, ho na le keketseho e itekanetseng ho DA ha mosali a hlahisoa ka mora skrini. Nakong ea ho qopitsa, MPOA DA e eketseha le ho feta (+ 50% ea basement), mme phello ena e hloka androgens (Hull et al., 1995; Putnam et al., 2003). Ha ho makatse hore ho banna ba tsohileng ba sa nyalaneng, MPOA DA ha e eketsehe (Hull et al., 1995). Ho thata ho toloka sephetho sena, hobane ho haella ha tokollo ea DA ho ferekantsoe ke ho se be teng hoa thobalano. Leha ho le joalo, tokollo ea DA ho MPOA e lumellana le tahlehelo ea ho tsofala mathoasong a nakoana a nakoana (Hull et al., 1995), le ka ho khutlisetsoa hoa liteko tsa thobalano tsa testosterone ho li-castrate tsa nako e telele (Du, Lorrain, le Hull, 1998; Putnam, Du, Sato, le Hull, 2001).

Ka har'a MPOA ea litoeba, li-androgenic le estrogenic metabolites tsa testosterone li bapala likarolo tse ikhethileng taolong ea ho tlolelana ha liphoofolo (Putnam et al., 2003; Putnam, Sato, Riolo, le Hull, 2005). Latency ea ho qapa ho qopitsa (ho hola kapa ho kenella hare) ke mokhoa o le mong oa khothatso ea thobalano. Monono oa ts'ebetso ea thobalano o tsotella li-estrogens, ka ho hlokomela MPOA nitric oxide synthase, eo ka lehlakoreng le leng e bolokang maemo a DA a basal. Li-castrate tse tšoeroeng ke estrogen li bonts'a maemo a phahameng a DA, a lumellanang haholo le bokhoni ba ho qala ho kopitsa. Le ha ho le joalo, ba hloleha ho bonts'a keketseho ea basali le tlhotlheletso ea ho lokolloa ha DA, e lumellanang hantle le ts'ebetso ea thobalano. Ka lebaka leo, ts'ebetso ea bona ea thobalano e ka tlase ho maemo a tlase. Ka lehlakoreng le leng, li-castrate tse tšoaroang ka androgen e seng aromatizable feela ha e bonts'e maemo a phahameng a DA, mme ba hloleha ho qala ho kopitsa. Bakeng sa ts'ebetso e tloaelehileng ea thobalano, ka hona, ho hlokahala li-estrogens le androgen ka bobeli. Ho etsa thobalano khafetsa ho hlalosoa e le mehato ea khafetsa ea lithunya, ho kenella le ho hlaba. Ke feela ha li-estrogener le li-androgen tse ling li nkeloa sebaka, banna ba tummeng ba bonts'a maemo a phahameng a DA (le mehato e mokhuts'oanyane ea latency) le li-DA tse eketsehang tsa basali le tse lateloang (le litekanyetso tse eketsehang). Ka mokhoa ona, li-estrogens ho MPOA li kenya letsoho ho susumetseng takatso ea thobalano, le li-estrogener le androgens tšebetsong ea thobalano.

Le ha testosterone e hlokahala bakeng sa tokollo ea MPOA DA nakong ea boits'oaro ba banna le bakeng sa ho ikatisa, ha ho na testosterone kapa ho nyaloa feela ho ka hohelang DA ho MPOA. Sebakeng seo, likhoele tsa chemosensory tse tsoang ho basali ba khethehileng le tsona li hlokahala bakeng sa tokollo ea DA ho MPOA. Lithakeng, chemosensory stimuli ke tsona maikutlo a mantlha a ho qala boitšoaro ba monna (Feie. 1). Lik'hemik'hale tsa Chemosensory li fetisoa ho tloha ho bulbsory ho ea ho MPOA ka li-nucleus tsa medial amygdaloid le mookotaba oa bethe ea stria terminalis, meaho e nang le AR e ngata le ER (Wood le Swann, 1999). Ho bona karolo ea litloaelo tsa chemosensory ho ho hohela batho ba bang DA, re lekantse MPOA DA nakong ea ha e ntse e nyaloa ka li-hamsters tse tona tse sa bonahaleng tse nang le unilateral olfactory bulbectomy (UBx, Triemstra, Nagatani, le Wood, 2005). Le ha ho tlosoa ha libate tse kopaneng ho felisa liketso tsa thobalano le ho lokolloa ha MPOA DA, bulbectomy e le 'ngoe ha e kena-kenane le ho ruruha. Phuputsong ena, qopitso e hlohlellelitse tokollo ea MPOA DA ha e lekantsoe mokonteraka ho bulb e entsoeng ka lesapo la litlolo, empa eseng ho ipsilateral hemisphere (Feie. 2). Liphetho tse tšoanang li ile tsa bonoa litotong tsa banna tse nang le marapo a medy amygdala (Dominguez, Riolo, Xu, le Hull, 2001). Phuputsong e amanang le ena, ts'usumetso ea lik'hemik'hale ea amygdala ea medial ho likhoto e hlohlellelitse tokollo ea MPOA DA e lekanang le eo nakong ea ho qopitsa (Dominguez le Hull, 2001). Ha li kopantsoe hammoho, lintlha tsena li fana ka maikutlo a hore testosterone e etsa tikoloho e lumellang e lumelle maikutlo a kantle a maikutlo ho fihlela MPOA le ho susumetsa tokollo ea DA nakong ea ho kopitsoa.

   

Feie. 2

DA e lekantsoe ho tsoa ho li-dialysates tsa MPOA nakong le ka mor'a ho ts'oaroa ka hamsters ea banna, e hlahisitsoeng e le liperesente tsa tokollo ea mantlha. TOP: Kusho ± Ho lokolloa ha SEM DA taolong (e ntšo, n = 11) le DA ka karolelano e lekantsoeng ho tloha ho dialysates tsa MPOA nakong le kamora ho nyaloa ho li-hamsters tsa banna, tse hlahisitsoeng e le liperesente tsa tokollo ea mantlha. TOP: bolela ± SEM DA e lokolloe taolong (e ntšo, n = 11) le ba batona ba bulbectomized (ba basoeu, n = 6). BOTTOM: bolela release Ho lokolloa ha SEM DA ho banna ba nang le unilateral olfactory bulbectomy contralateral (batsho, n = 8) kapa ipsilateral (tšoeu, n = 9) ho probe ea dialysis. Shading e emela sampole e bokelloang nakong ea ho tlolelana. Asterisk e bontša phapang ea bohlokoa ha e bapisoa le motheo. (Ho tloha Triemstra, JL, Nagatani, S., le Wood, RI, 2005).

Qetellong, boitšoaro ba thobalano le meputso e meng ea tlhaho e etsa hore ho be le meputso ea neural. Potoloho ea mesocorticolimbic DA e na le sebaka sa ventral tegmental (VTA), li-nucleus accumbens (Acb), le preortalal cortex (Pfc). Litopo tsa lisele tsa Dopamine tse lulang morerong oa VTA li lula hantle ho Acb le Pfc (Koob le Nestler, 1997). Litekong, DA e lokolloa ka har'a Acb nakong ea thobalano (Pfaus, Damsma, Nomikos, Wenkstern, Blaha, Phillips, le Fibiger, 1990). Lithethefatsi tse ngata tsa tlhekefetso li boetse li sebetsa tsamaisong ea mesolimbic DA ho eketsa tokollo ea DA (amphetamines) kapa ho thibela DA reuptake (cocaine, Di Chiara le Imperato, 1988), ka hona ho tiisa thepa ea bona e lemalloang. Ka mokhoa ona, testosterone e na le monyetla oa ho ama tokollo ea DA ho Acb ka bobeli ka ntlafatso ea eona ea boitšoaro ba thobalano, le ka liketso tsa eona e le lithethefatsi tsa tlhekefetso (bona ka tlase).

Bopaki ba hajoale bo fana ka maikutlo a hore sisteme ea mesocorticolimbic DA e kholo nakong ea bohlankana. Methapo ea Acb DA fiber e eketseha haholo nakong ea bocha ho li-germils, e fana ka tlhahiso ea hore phapang ea bohlokoa ea likhakanyo tsa dopaminergic ho Acb li etsahala nakong ea bohlankana.Lesting, Neddens, le Teuchert-Noodt, 2005). Ho feta moo, ho kenella ka dopaminergic ho GABA (γ-aminobutyric acid) -seli tsa "cortex" tsa "medical prefrontal cortex" ho ntlafatsoa le ho fetoloa ke lits'ebeletso tsa serotonergic nakong ea kholo ea "pub"Benes, Taylor, le Cunningham, 2000), le ho qhekella ha androgens ho likhoto tsa batho ba baholo ho lebisa ho phetoho ea letsoalo la dopaminergic axon kahara cortex ea pele (Kritzer, 2003). Pfc, Acb, le VTA ha li na AR kapa ER tse fokolang, leha ERβ e le teng ho VTA (Shughrue et al., 1997). Ka hona, ho bonahala ho ka etsahala hore androgens e ame ts'ebetso ea mesocorticolimbic DA ka litumellano tse tsotellang tsa androgen kapa ka ERβ ho VTA joalo ka hypothalamus (Handa et al., Makasine ona). Lintlha tsa rona li bonts'a lisele tse nang le bothata ba androgen porojeke ea hamsters ea banna ho VTA ho tsoa mehahong e amanang le boits'oaro bo nang le bothata ba steroid. Mohlala, ka bobeli MPOA le "nucleus" ea stria terminalis (BST) e na le palo e kholo ea lisele tse ntle tse sebetsang tse hlahisang VTA (Sato le Wood, 2006). Porral pallidum, sepheo se ka sehloohong sa Acb efferent (Zahm le Heimer, 1990), hape e na le lisele tse ngata tse ntle tsa AR tse hlahisang VTA. Maikemisetso ana a fana ka monyetla oa ho androgens ho fetola tšebetso ea sisteme ea mesocorticolimbic DA.

Mokhatlo o itšetlehileng ka Steroid nakong ea bohlankana

Pono ea moetlo ea ketso ea li-hormone mabapi le boits'oaro ba bocha e thehiloe ho litlamorao tse sebetsang tsa lihormone tsa steroid, tse buang ka bokhoni ba li-steroid ba ho tsamaisa boitšoaro maemong a ikhethileng a sechaba ka ketso e kahare ho lisele tse lebelletsoeng ho li-circuits tsa neural tse ka tlase ho boitšoaro. Litlamorao tsa ts'ebetso li lieha ho feta ka kutloisiso ea hore li tla ebe li tsamaisana le boteng le ho ba sieo ha li-hormone, mme hangata li amana le polelo ea boitšoaro ba batho ba baholo. Ka lehlakoreng le leng, litlamorao tsa mokhatlo li bua ka bokhoni ba li-steroid ba ho taka sebopeho sa tsamaiso ea methapo nakong ea kholo. Mokhatlo oa meralo o lula o le teng ka mehla, o phehella ho feta nako ea ho pepesetsoa li-hormone, 'me o tseba likarabo tsa neural le boits'oaro ho li-steroid botsofaling. Kutloisiso ea rona ea kamano e ntlafatsang lipakeng tsa tlhophiso le tšebetso ea lihormone tsa steroid e bile teng lilemong tse fetileng tsa 50. Phoenix le basebetsi-mmoho ba qalile ho etsa tlhahiso ea hore likarabo tsa batho ba baholo (li-activative) tsa lihormone tsa steroid li hlophisitsoe (li hlophisitsoe) ke lihormone tsa steroid nakong e kholo ea kholo ea kholo ea ntlafatso ea kelello.Phoenix, Goy, Gerall, le Monyane, 1959). Hamorao, Scott le basebetsi mmoho ba thehile motheo oa theoretical bakeng sa ho ba teng ha linako tse ngata tse mahlonoko bakeng sa mokhatlo o tsoelang pele oa tsamaiso ea methapo, mme ba hlokometse hore linako tse mahlonoko li ka etsahala hangata nakong ea phetoho e potlakileng ea ntlafatso (1974). Kamora nako, Arnold le Breedlove ba bontšitse hore mokhatlo o hlophisitsoeng ke boko ba marang-rang o ka ts'epahalang o ka hlaha kantle ho nako e tebileng ea ntlafatso (Arnold le Breedlove, 1985). Lilemong tse fetileng tsa 15, lipatlisiso li sebelisa mefuta e fapaneng ea liphoofolo le mekhoa ea boits'oaro e hlakisa hore boko ba bongoana bo ela hloko litlamorao tsa ts'ebetso le mokhatlo tse hlophisitsoeng tsa gonadal steroids (e lekantsoe ho Sisk le Zehr, 2005). Hape, joalo ka linako tse ling tsa phetoho e potlakileng ea kholo ea bocha, bocha bo emela monyetla o hlalositsoeng oa monyetla oa ho nchafatsa kelello e thehiloeng ke steroid.

Mosebetsi oa rona o sebelisang hamster e le mohlala oa phoofolo o fana ka bopaki ba hore boitšoaro ba banna ba basali bo fetotsoe ke li-steroid nakong ea bohlankana.Schulz, Menard, Smith, Albers, le Sisk, 2006; Schulz le Sisk, 2006). Pele ho kena bohlankaneng, kalafo ea testosterone e ke ke ea kenya tšebetsong boitšoaro ba thobalano ho hamsters, e fana ka tlhahiso ea hore lits'ebetso tsa maturational tse fanang ka li-circuits tsa neural tse amehang ts'ebetsong kapa mokhatlong o sebetsang oa lihormone tsa steroid ha li e-so etsahale (Meek et al., 1997; Romeo, Richardson, le Sisk, 2002a). Ka lehlakoreng le leng, le hoja polelo e totobetseng ea boitšoaro ba banna ha e se e le motho e moholo ha e hloke ho hang ho ba teng ha li-gonadal steroid nakong ea bocha, pontšo e kholo ea boitšoaro e etsa joalo. Ha ho bapisoa boits'oaro ba botona ho banna ba hahiloeng pele ho pubertally (NoT@P) kapa postpubertally (T@P) ebe ba phekoloa ka testosterone ha ba se ba holile, prepubertal NoT@P castrates bonyane ba na le khaello ea 50% boitšoarong ba banna ha ba bapisoa le ba batona ba khaotsoeng kamora lilemo tsa bocha. (Feie. 3, Schulz, Richardson, Zehr, Osetek, Menard, le Sisk, 2004). Ntle le moo, liphoso tsa boitšoaro ba ho ba le bana li nka nako e telele, 'me li ke ke tsa felisoa ka kalafo ea testosterone ea nako e telele kapa ke boiphihlelo ba ho ba le thobalano ha motho a le moholo.Schulz et al., 2004). Ka mokhoa o ts'oanang, kamora kalafo ka estrogen le progesterone, banna ba NoT@P ba bonts'a li-latency tse khutšoane tsa lordosis le nako e telele ea lordosis ho feta ba batona ba lahliloeng e le batho ba baholo.Schulz et al., 2004), ho fana ka maikutlo a hore li-castubertal castrate ha li nyenyefatsoe ho feta banna ba pepesitsoeng testertal testosterone.

   

Feie. 3

Palo ea li-intromission tse bonts'itsoeng ke li-hamster tsa banna tse entsoeng pele ho bohlankana (NoT@P) kapa ka mor'a ho kena bohlankaneng (T@P). Banna bohle ba ne ba e-na le testosterone-primed ho ba batho ba baholo, 7 wk ka mor'a gonadectomy le beke pele ho tlhahlobo ea pele ea boitšoaro. Banna ba T@P ba bonts'itse li-intromissions tse ngata haholo ho feta tsa banna ba NoT@P le kamora liphihlelo tse tharo tsa thobalano le mosali ea amohelang. (Lintlha tse sa phatlalatsoang tse tsoang ho liphoofolo tse ruuoang ka har'a Schulz, KM, Richardson, HN, Zehr, JL, Osetek, AJ, Menard, TA, le Sisk, CL, 2004)

Ho ka etsahala hore ebe banna ba NoT@P ba na le ts'usumetso e fokolang ea thobalano. Tsela e 'ngoe ea ho araba potso ena ke ho bapisa li-latencies ho etsa lipatlisiso tsa ano-genital (AGI) le ho phahama pakeng tsa banna ba gonadectomized pele ho (NoT@P) le ka mor'a ho kena bohlankaneng (T@P). Haeba tšusumetso ea thobalano e itšetlehile ka ho pepeseha ha lihomone tsa gonadal nakong ea bocha, re ka bolela esale pele nako e telele ea ho kopanela boitšoarong ba thobalano ho banna ba NoT@P. Ehlile, ka ho pepesetsoa khafetsa ho basali ba estrous, banna ba NoT@P ba nka nako e telele ho qala AGI le ho nyoloha ha ba bapisoa le ba batona ba T@P.Feie. 4). Kahoo, ntle le ho hlophisa likarolo tsa ts'ebetso ea thobalano, ho bonahala eka lihomone tsa pubertal le tsona li hlophisa likarolo tse khotsofatsang tsa boitšoaro ba thobalano. Ho ts'ehetsa monyetla ona, tsamaiso e bohareng ea DA agonist apomorphine ha e se e holile e khutlisetsa boits'oaro bo ntseng bo eketseha ba banna ba NoT@P ho maemo a tloaelehileng a batho ba baholo, ho fana ka maikutlo a hore testosterone nakong ea bocha hangata e hlophisa li-circuits tsa dopaminergic neural (Salas-Ramirez, Montalto, le Sisk, 2006). ). Leha ho le joalo, ho na le lipotso tse ngata tse thahasellisang. Na setopo sa banna sa NoT@P se ka etsetsa mosali e motšehali kapa se ka etsa khetho ea sebaka se nang le maemo bakeng sa sebaka sa ho beletsana? Lipatlisiso tsa nako e tlang li tla hlahloba karolo ea lihomone tsa pubertal ho hlophisa tšusumetso ea thobalano le ts'ebetso ea thobalano.

   

Feie. 4

Lipatlisiso tsa Anogenital (AGI) le nako tse bonts'itsoeng ke li-hamster tsa banna tse entsoeng pele ho bohlankana (NoT@P) kapa ka mor'a ho kena bohlankaneng (T@P). Banna bohle ba ne ba le testosterone-primed ho ba batho ba baholo 7 wk ka mor'a gonadectomy le beke e le 'ngoe pele ho tlhahlobo ea pele ea boitšoaro. Banna ba A. T@P ba bonts'itse ho lieha ha AGI ka mokhoa o ts'oanang litekong tse tharo le mosali e motšehali, athe banna ba NoT@P ba ile ba eketsa tieho ea AGI nakong ea tlhahlobo ea boraro le mosali ea estrous. B. T@P ba batona ba fokotsitse ho lieha ha nako ho pholletsa le liteko tse tharo tsa boitšoaro ka mosali e motšehali, athe banna ba saT@P ha ba bontše phetoho ho mount latency litekong tse tharo tsa boitšoaro. Lintlha tsena li fana ka maikutlo a hore li-hormone tsa pubertal gonadal li na le litlamorao tse tšoarellang, tse thusang ho khothaletso ea banna ba baholo ho etsa thobalano le mosali. (Lintlha tse sa phatlalatsoang tse tsoang ho liphoofolo tse ruuoang ka har'a Schulz, KM, Richardson, HN, Zehr, JL, Osetek, AJ, Menard, TA, le Sisk, CL, 2004).

Likarabo tsa boitšoaro bo botle esale pele ho li-steroid

E 'ngoe ea lipuzzle tse tšoarellang tsa ntlafatso ea boitšoaro ba bongoaneng ke hobaneng ts'ebetso ea boitšoaro ba botona ho arabela ponahalong ea steroid e bonts'oa ho li-hamsters tsa pele ho monna. Haeba maemo a tlase a androjeni pele ho nako ea bokhachane a fokotsa tlhahiso ea botona ba botona ba botšehali ho banna ba pelehi, joale ho tlatsana le li-androjeni tsa nako e telele ho banna ba tlileng pele ho nako ho lokela ho etsa hore motho a ratoe. Sena ha se sa ba joalo (Meek et al., 1997; Romeo, Cook-Wiens, Richardson, le Sisk, 2001; Romeo, Wagner, Jansen, Diedrich, le Sisk, 2002b), ho sa tsotelehe taba ea hore palo le ho ajoa ha AR le ER potolohong eohle ea ho tsofala lia tšoana ho li-castellant tsa kalafo tse fetisitsoeng ka li-hormone le batho ba baholo (Meek et al., 1997; Romeo, Diedrich, le Sisk, 1999; Romeo et al., 2002a). Ka hona, ho bonahala hore androgens le AR lia hlokahala empa ha li lekane bakeng sa ho bontša boitšoaro ba monna ba thobalano.

Boiteko ba ho tseba lintho tse fokotsang thobalano pele motho a kena bohlankaneng bo se bo kopane. Likarabo tsa Fos ho li-chemosensory cues tse tsoang ho basali ba batšehali li tšoana ho li-hamsters tsa banna ba baholo le ba baholo (Romeo, Parfitt, Richardson, le Sisk, 1998). Lintlha tsena li bonts'a hore mekhoa ea ho fetisa mehopolo ea maikutlo e holisoa pele ho nako ea ho kena bohlankaneng. Kahoo, bana ba batona ba khona ho bona likhechana tsa chemosensory ho basali; moo ba fapaneng le batho ba baholo ke ka tsela eo ba arabelang ka eona mekhoeng eo. Tlhaloso e 'ngoe e ka ba teng ke hore banna ba tlileng pele ho lenyalo ha ba khothalletsoe ho etsa thobalano. Re fumane hore li-hamsters tsa pele tsa banna ha li bonts'e likarabo tse eketsehang tsa dopaminergic ho MPOA ho arabela li-pheromones tsa basali, athe banna ba baholo ba nang le thobalano ba nang le thobalano ba bonts'a likarabo tse matla tsa MPOA dopaminergic karolong e tšoanang.Feie. 5, Schulz, Richardson, Romeo, Morris, Lookland, le Sisk, 2003). Ka mokhoa o ts'oanang, ba batona ba pelehi ba sitoa ho bonts'a kholo ea batho ba baholo ea ho potoloha testosterone kamora ho pepesetsoa li-pheromones tsa basali (Parfitt, Thompson, Richardson, Romeo, le Sisk, 1999). Ka hona, li-pheromones tsa basali li bonahala e le tšusumetso e se nang boikemelo ea likarabo tsa methapo-kutlo le neuroendocrine ho batho ba baholo, empa eseng banna ba tlang pele ho sena, ba fana ka maikutlo a hore boteng ba maikutlo ana a susumetsang maikutlo a maikutlo sechabeng bo fetoha holima nts'etsopele ea "pubertal" Ntle le moo, le ha testosterone e nolofalletsa mosali hore a be le mosali ho banna ba tlileng pele ho sena, sephetho sena se ipapisitse le hore na monna o kile a pepesetsoa mosali ea tsofetseng kapa che. Mohlomong ka mokhoa o makatsang, kalafo ea testosterone e fokotsa ho latsoa le ho eketsa nako ea AGI feela ho banna ba thobalano le naïve ba pelehi ba pelehi (Feie. 6). Ho feta moo, banna ba tlileng pele ho nako ba kileng ba ba le boiphihlelo bo le bong ba pele ho nako ea mosali le litšebelisano tse khutšo tsa AGI ho feta banna ba sebelisanang le basali ba amohelang ka lekhetlo la pele (Feie. 6). Lintlha tsena li fana ka maikutlo a hore ho sebelisana le mosali oa moshemane ho na le maikutlo a mangata ho fapana le ho putsa pele ho kena bohlankaneng, ka tsela eo, ho felisoa ka litlamorao tsa testosterone ho AGI nakong ea litšebelisano tse latelang le mosali. E tla ba ho khahlisang ho tseba hore na litlamorao tse mpe tsa ho pepesetsoa ho basali ba batšehali li tswela pele ho ba bohlankana le ho ba motho e moholo, haholoholo ha ho pepesetsoa nako e telele ho basali ba batšehali nakong bocha hangata bo nolofalletsa polelo ea boits'oaro ba monna (Molenda-Figueira, Salas-Ramirez, Schulz, Zehr, Montalto, le Sisk, 2007).

   

Feie. 5

Karabelo ea dopaminergic ea prepubertal le ea batho ba baholo ba malebela a dopaminergic ho li-pheromones tsa basali tse fumanehang mokokotlong oa botšehali. Batho ba baholo ba banna ba bonts'a keketseho ea tšebetso ea dopaminergic ea MPOA ka ho pepesetsoa maqhubu a basali, athe banna ba tlang pele ho nako ba sa bonts'e likarabo tse eketsehang tsa MPOA dopaminergic ho li-pheromones tsa basali. (Fubella ho tsoa ho Schulz, KM, Richardson, HN, Romeo, RD, Morris, JA, Lookland, KJ, le Sisk, CL, 2003).

 

   

Feie. 6

Boemo ba li-hamsters tsa pele ho pele ho etsa lipatlisiso tsa lefutso le mosali ea haufi le nako eohle e sebelisitsoeng ho fuputsa mosali nakong ea puisano ea motsotso oa 15. K. Thobalano e sa tsotelleng ea testosterone e tšoeroeng ke baimana ba pelehi e bontša bokhuts'oane ba AGI ho feta ba batona ba sa sebetseng ba pelehi ba pepileng, empa boiphihlelo ba thobalano bo tlosa litlamorao tsa testosterone ho latellano ea AGI. B. Ba batona ba hlekefelitsoeng ka thobalano ba testosterone ba hlekefetsoang ka thobalano ba bonts'itse nako e teletsana ho feta banna ba sa tšoaroang ka letho, empa testosterone e bile le tšusumetso e nyane ho nako ea AGI ho banna ba nang le bohlola. Lintlha tsena li fana ka maikutlo a hore boiphihlelo ba pele ba thobalano bo fokotsa tšusumetso ea ho etsa lipatlisiso tsa basali. (Lintlha tse sa fetoloang ho tsoa ho lithuto tsa liphoofolo ho Schulz, KM, Richardson, HN, Zehr, JL, Osetek, AJ, Menard, TA, le Sisk, CL, 2004)

 

Le ha kalafo ea preubertal androgen e sa khone ho kopitsa ho kopitsa, mosebetsi oa morao-rao o tsoang laboratoring ea rona o bonts'a hore tsamaiso ea methapo ea hamster e ela hloko liketso tsa ho hlophisa tsa testosterone mabapi le boits'oaro pele ho nako ea bocha (Schulz, Zehr, Salas-Ramirez, le Sisk, 2007). Matsatsi a ho fallisoa le 19 matsatsi a ho pepeseha hoa testosterone pele kapa nakong empa eseng ka mor'a bocha ho nolofalitse boitšoaro bo ntseng bo eketseha ha testosterone e nkeloa sebaka ea ho ba motho e moholo. Tse tona li pepesitsoe testosterone preubertally li boetse li bonts'a maqhubu a ho ba motho e moholo ho feta banna ba pepesitsoeng testosterone nakong ea bokhachane kapa kamora ho emisa (Schulz et al., 2007). Lintlha tsena li fana ka maikutlo a hore bokhoni ba testosterone ba ho hlophisa li-circular tsa neural tsa boitšoaro bo fokotseha ka lilemo, le hore nako ea bocha e tšoaea pheletso ea nako e kholo ea kamora ho pepeseha ea testosterone.

Pharmacologic androgens

Lintlha tse ka pele li fana ka maikutlo a hore li-steroid tsa morao-rao tsa gonadal li ntlafatsa boitšoaro bo susumetsoang nakong ea bocha. Joale, ho etsahalang haeba motho a itlhomme androgens maemong a ho fihlela ho 100x li-standard tsa physiologic? Ena ke bothata ba tlhekefetso ea anabolic-androgenic steroid (AAS) (e lekantsoeng ka Brower, 2002; Clark le Henderson, 2003). Ho ts'oaroa ha bokhutšoanyane ho loketse mona: li-AAS tsohle li tsoa ho testosterone, li-AAS kaofela li na le skeleton ea khase e nang le mehele e 4 e kentsoeng, boholo ba eona e na le likoloi tsa 19. AAS e sebelisoa haholo-holo bakeng sa litlamorao tsa tsona tsa anabolic (misuli-building). Leha ho le joalo, joalo ka ha lebitso la bona le bolela, AAS le eona e na le thepa ea androgenic. Testosterone ke khetho e bohlale lithutong tsa liphoofolo bakeng sa ho hlahloba mekhoa ea mantlha ea moputso oa androgen. E ntse e le khetho e tsebahalang bakeng sa basebelisi ba batho, hangata ka mokhoa oa li-estosterone tse sebetsang ka nako e telele joalo ka testosterone propionate. Ho 2006, testosterone e ne e le ntho e le 'ngoe e neng e thibetsoe ka ho fetisisa e fumanoeng litekong tsa moroto li-laboratories tse amoheloang ke WADA (WADA, 2006). Testosterone e ikarabella bakeng sa karoloana e kholo ka ho fetisisa (34%) ea liteko tsa moroto tse sebetsang tsa AAS ho lipapali tsa Liolimpiki tsa 2000 tsa Sydney (Van Eenoo le Delbeke, 2003). Ka mokhoa o ts'oanang, litekong tsa moroto tsa basebelisi ba AAS, 41% e fumanoe e le testosterone hantleBrower, Catlin, Blow, Eliopulos, Beresford, 1991). Ka tekanyetso e phahameng, AAS e hlahisa liphetoho tse kholo tsa boitšoaro. Haholo-holo, ka lebaka la kamano ea bona e haufi le testosterone, ts'ebeliso ea AAS lilemong tsa bocha e ka bonahala e ama seemo se tloaelehileng sa steroid ea ts'ebetso ea methapo ea bongoana e kenyelletsang, ho kenyelletsa palo, nako le mofuta oa tlhahiso ea li-steroid.

Joalo ka lithethefatsi tse ling tse seng molaong, tlhekefetso ea motho ea AAS ke bothata ba bohlankana. Ho latela lipatlisiso tsa malapa tsa naha tsa 1994 mabapi le Ts'ebeliso ea Lithethefatsi (SAMHSA / OAS, 1996), li-steroid li sebelisa litlhōrō tsa ho ba lilemong tsa bocha lilemong tsa 18. Ho feta moo, ho tlhahlobo ea tlhahlobo ea bokamoso (Johnston, O'Malley le Bachman, 2003), nako ea bophelo ea tšebeliso ea steroid har'a batho ba baholo ba sekolo se phahameng (2.7%) e ne e ka bapisoa le seo ka lebaka la ufa oa koae (3.5%) kapa heroin (1.4%). Ts'ebeliso ea Steroid e atile le ho feta lilemong tse nyane: 2.5% ea baithuti ba karolelano ea 8th (13-14 lilemo) ba sebelisitse li-steroid, tse tšoanang le ts'ebetso ea bohlanya (2.5%) le tšebeliso ea heroin (1.6%). Tloaelo ena mabapi le tšebeliso ea AAS lilemong tsa bocha e tšoenyeha haholo ka lebaka la ho tšoenyeha ka 1) hore bacha ba ka ba kotsing e kholo ea ho hlekefetsoa ha AAS, le 2) hore ho pepesetsoa bongoana ho AAS maemong a pharmacologic ho na le menyetla ea ho fetola kholo ea phetoho e tloaelehileng ea kelello le boits'oaro ba ho hlahisa likarabo tse fetelletseng tsa morphological le boits'oaro, ka mokhoa o hlakileng le o sa foleng.

Ho ba mabifi ho sa lokelang ke karabelo ea boitšoaro hangata e amanang le tlhekefetso ea motho ea AAS. Litlalehong tsa linyeoe tse sebelisitsoeng, tšebeliso ea steroid e kentse letsoho lipolaong tse 'maloa tse mabifi (Moqapi le mosebetsi, 1989; Mopapa le Katz, 1990; Mopapa, Kouri, Powell, Campbell, le Katz, 1996; Schulte, Hall, le Boyer, 1993). Liphuputsong tsa basebelisi ba hona joale ba AAS, mabifi le ho se ts'oarehe e bile litla-morao tse atileng haholo tsa ts'ebeliso ea ts'ebeliso ea AAS (Bond, Choi, le Mopapa, 1995; Galligani, Renck, le Hansen, 1996; Midgley, Heather, le Davies, 2001; Parrott, Choi, le Davies, 1994; Perry, Kutscher, Lund, Yates, Holman, le Demers, 2003). Leha ho le joalo, ha ho fanoa ka mefuta e mengata ea tlhahiso ea androgen, matšoao a fapaneng a kelello, le monyetla oa ho se sebetse hantle kelellong, ho thata ho tseba karolo e tobileng ea AAS maemong ana a mabifi a motho. Liphetho ho tsoa liphuputsong tse tlang ho ba baithaopi ba batho ba fumanang liente tsa AAS li tsoakiloe: Tricker et al (1996) 'me O'Connor et al (2004) ha hoa tlaleheloa hore ho na le keketseho ea boits'oaro bo halefileng ha lithuto tse ling li bone ho eketseha ha mabifi (Daly, Su, Schmidt, Pickar, Murphy, le Rubinow, 2001; Hannan, Friedl, Zold, Kettler, le Plymate, 1991; Kouri, Lukas, Mopapa, le Oliva, 1995; Mopapa le Katz, 1994; Su, Pagliaro, Schmidt, Pickar, Wolkowitz, le Rubinow, 1993). Le ha ho le joalo, ho bohlokoa ho hopola hore tekanyetso e fuoang baithaopi ba batho e tlaase haholo ho feta litekanyetso tse khothalletsoang ho liwebsaete tsa kaho ea 'mele, le nako ea kalafo hangata ha e khuts'oane. Ka hona, ho leka-lekana, ho bonahala ho loketse ho fihlela qeto ea hore AAS e na le monyetla oa ho ntlafatsa boits'oaro ba boloi, bonyane ho batho ba kotsing. Mopapa et al (1994) o fumane hore matšoao a kelello a AAS a hlahisa kelello ho batho ba hlaselehang habonolo.

Lithuto tsa liphoofolo li boetse li fane ka bopaki bo susumetsang bakeng sa mabifi a susumetsoang ke AAS. Bahlahisi ba batona ba lilemong tsa bocha ba phekoloa ka mokhoa o sa tloaelehang ka li-steroid tsa boleng bo phahameng ba na le lisele tse khuts'oane tsa tlhaselo le ho loma ho motho ea kenang molemong oa monna ha ba bapisoa le ba batona (Harrison, Connor, Nowak, Nash, le Melloni, 2000; Melloni, Connor, Hang, Harrison, le Ferris, 1997). Ka mokhoa o ts'oanang, moferefere o bonolo (mohatla-nyane) o hlahisa keketseho e sa khaotseng ea mabifi ho likhoto tsa banna ba lilemong tsa bocha, ho kenyelletsa le mabifi ho basali (Cunningham le McGinnis, 2006). Ho tšoenyang le ho feta, ho pepesehela bocha ho AAS ka hamsters ho baka keketseho e sa feleng ea boits'oaro bo botle bo phehellang kamora hore tšebeliso ea steroid e khaoe (Grimes le Melloni, 2006). Liphetoho tsena tsa boits'oaro li tsamaisana le ho nchafatsa bo sa khaotseng ba neural circry ho anterior hypothalamus. Haholo-holo, ho pepesetsoa ha AAS ea lilemong tsa bocha ka hamsters ho ntlafatsa arginine vasopressin (AVP, Grimes le Melloni, 2006) le li-serotonin tsa serotonin le li-serotonergic 5HT1A le li-receptors tsa 5HT1B (Ricci, Rasakham, Grimes le Melloni, 2006). Ha rea ​​lokela ho makala hore ebe AAS e fetotse maemo a boko ba AR le. Ho pepeseha ho sa feleng ka testosterone kapa nandrolone ho nyolla sele ea nyutlelie ka litoeba tse tona (Menard le Harlan, 1993; Wesson le McGinnis, 2006). Kahoo, ho na le monyetla oa hore AAS e ntlafatse boits'oaro bo itšetlehileng ka androgen ka bobeli ka ho tlatsetsa androgens ea endo native le ka ho eketsa karabelo ea androgenic ka polelo e eketsehang ea AR.

Ha ho bapisoa le boitšoaro ba agonistic, AAS e na le phello e fokolang ho boitšoaro ba mating ka litoeba tsa banna, mme karabelo e ipapisitse le steroid e itseng e sebelisitsoeng (e lekantsoe ho Clark le Henderson, 2003). Ka hamsters tse tona tse jang testosterone ka tharollo ea molomo, li-ejaculations li ile tsa eketseha ka tsela e itšetlehileng ka lethal dose (Wood, 2002). Leha ho le joalo, ha ho na testosterone kapa nandrolone e ntlafalitseng mating litsing tsa banna ba lilemong tsa bocha. Stanozolol, e leng AAS e seng matla haholo e nang le ts'ebetso e nyane ea androgenic, ha e le hantle e sitisitse botsitso le mabifi (Farrell le McGinnis, 2003), mohlomong ka ho fokotsa maemo a androgen a androgen.

Ho bohlokoa haholo ho hlokomela hore li-hamsters tsa lilemong tsa bocha le tse kholo li ka bonts'a likarabo tse fapaneng tsa boitšoaro ho pepesong ea AAS. Le ha AAS e ntlafalitse mokhoa oa botaki ho banna ba lilemong tsa bocha, kalafo e tšoanang ho ba motho e moholo e hlahisitse keketseho e fokolang ea boits'oaro bo mabifi mme ea fokolisa haholo boitšoaro ba thobalano (Salas-Ramirez, Montaldo le Sisk, 2008). Sena se lumellana le mohopolo oa bocha e le nako e mahlonoko bakeng sa ketso ea androgen. Ho feta moo, joalo ka ha li-hamsters tsa banna ba baholo li fumana mamello ho testosterone ea khale (Peters le Wood, 2005), re lumela hore banna ba ntlafatsang ba na le mamello ho testosterone ha ba hola. Kahoo, litlamorao tsa phetoho ea AAS ho holisa kholo ea bacha, le ho pepesetsoa bocha ba AAS ho ka baka tšenyo e feteletseng le boits'oaro ba thobalano bo ka phehellang ho ba motho e moholo.

Ho matlafatsa litlamorao tsa androgens

Ho nyarana le ho loana ho na le moputso o mong le o mong (bonyane haeba u hlōla ntoa). Lirata tse tona li tobetsa lever khafetsa hore li kopane le mosali (Everitt le Stacey, 1987). Ka mokhoa o ts'oanang, litoeba tse tona le tse tšehali li tla theha sebaka se ikhethileng (CPP) bakeng sa libaka tseo pele li hapileng lintoa (Martinez, Guillen-Salazar, Salvador, le Simone, 1995; Meisel le Jopa, 1994). Haeba AAS e ka ntlafatsa boits'oaro bo botle ba sechaba kaholimo ho maemo a tloaelo a bonoang ho banna ba gonad-intact, hoa utloahala ho lebella hore testosterone ka boeona e ka ba e putsa. Sena se lekoa ho sebelisa mefuta e 'meli ea liphoofolo e thehiloeng hantle bakeng sa moputso le matlafatso: CPP le boits'oaro. Liphetho tsa lithuto tsena li bonts'a hore testosterone e matlafatsa maemong a liteko moo litlamorao tsa anabolic le ts'ebetso ea lipapali li sa sebetseng. Ka CPP, ntho ea tlhahlobo e kopantsoe khafetsa ka tikoloho e ikhethileng (mohlala, kamore e itseng ho lisebelisoa tsa liteko). Hang ha phoofolo e hokahanya ntho e matlafatsang ea tlhahlobo le tikoloho eo, o tla batla tikoloho leha a se na moputso. Litlaleho tsa pele tsa moputso oa androgen liphoofolong tsa laboratori li sebelisitse liente tsa systemic tsa testosterone ho kenya CPP ho litoeba tsa banna (Arnedo, Salvador, Martinez-Sanchis, le Gonzalez-Bono, 2000; Arnedo, Salvador, Martinez-Sanchis, le Pellicer, 2002) le likhoto (Alexander, Packard, le Hines, 1994; de Beun, Jansen, Slangen, le Van de Poll, 1992). Kamora moo, laboratori ea rona e ile ea sebelisa boits'oaro ba testosterone ho bonts'a ntlafatso ea androgen (Johnson le Wood, 2001). Re fumane hore li-hamsters tsa banna li tla sebelisa ka boithaopo litharollo tsa molomo oa testosterone ka ho sebelisa liteko tse peli tsa 2 tsa botlolo ea joala le joala bo khothalletsoang. Lithutong tsa morao-rao, re bonts'a boits'ebetso ho li-rats tsa banna le hamsters (Wood, Johnson, Chu, Schad, le Boithati, 2004). Ho tsamaisoa kahare ho tlose ho ka baka litlamorao tse hohelang tsa tatso kapa ho itjella ka gut ho latela ho ja ha androgen.

Boemong ba tlhekefetso ea AAS, ho bohlokoa ho khetholla lipakeng tsa litlamorao tsa pherekano le tsa perigheral tsa androgens. Kaha testosterone e na le litlamorao tse pharalletseng ho pholletsa le 'mele, ho ka pheha khang ea hore moputso le ho matlafatsoa ka liente tsa testosterone tsa systemic ke tsa bobeli ho liketso tsa testosterone tsa methapo ea methapo ea kutlo le androgenic. Ka mantsoe a mang, mohlomong testosterone e fokotsa mokhathala oa mesifa mme e ntlafatsa ts'ebetso e kopanetsoeng e le hore liphoofolo li ikutloa betere. Ho joalo, tlhaloso ena e sebelisitsoe ho lingoliloeng tsa bongaka (le hoja ho se na bopaki ba liteko) ho hanyetsana le monyetla oa ho its'epa le ho lemalla AAS (DiPasquale, 1998). Leha ho le joalo, Packard et al (Packard, Cornell, le Alexander, 1997) e bonts'itse hore liente tsa testosterone ka kotloloho bokong ba rat li ka kenyelletsa CPP. Ka mokhoa o ts'oanang, laboratori ea rona e bonts'itse ts'ebetso ea testosterone ea intracerebroventricular (icv) ho li-hamsters tsa banna (Wood et al., 2004). Intracerebral CPP le tsamaiso ea icv e nang le testosterone e ngangisana bakeng sa liphofu tse bohareng tsa ho matlafatsa le ho matlafatsa tsa androgen.

Hoa hlokomeleha hore ho matlafatsoa ha testosterone ha ho hlile ha ho latele mekhoa e tšoanang e neng e thehiloe pele bakeng sa litlamorao tsa steroid ka boitšoaro ba thobalano. Joalokaha ho hlalositsoe pejana, MPOA ke sebaka sa mantlha sa tlhophiso ea boitšoaro ba batho ba batona kapa ba batšehaliHull, Meisel, le Sachs, 2002). Ka hamsters, MPOA e na le li-receptor tse ngata tsa steroid, le li-testosterone tsa MPNA ho MPOA li khutlisetsa liketso tsa thobalano ho li-castrate tsa nako e telele (Wood le Swann, 1999). Nako ea nako ea litla-morao tsena tsa steroid e ea lieha: boitšoaro bo ntseng bo eketseha bo phehella libeke kamora ho orchidectomy, 'me ho pepesetsoa ha steroid ho hlokahala ho khutlisa ho ruruha ho li-castrate tsa nako e telele (Noble le Alsum, 1975). Leha ho le joalo, liente tsa testosterone ho MPOA ea likhoto tsa banna li sitoa ho susumetsa CPP (King, Packard, le Alexander, 1999). Sena se fana ka maikutlo a hore libaka tse ling tsa boko li bohlokoa bakeng sa ho matlafatsoa ha androgen.

Ka lehlakoreng le leng, likhoto tsa banna li tla theha CPP bakeng sa liente tsa testosterone ho Acb (Packard et al., 1997). Joalo ka lithethefatsi tse ling tsa tlhekefetso, DA e kanna ea ba neurotransmitter ea bohlokoa ea ntlafatso ea testosterone: CPP e hlahisoang ke ente ea testosterone ea testosterone e koetsoe ke D1 le D2 dopamine receptor antagonists (Schroeder le Packard, 2000). Leha ho le joalo, ho fapana le lithethefatsi tse ling tsa tlhekefetso, lithuto tsa rona ka hamsters li fana ka maikutlo a hore testosterone ha e khothalletse ho lokolloa ha Acb DA (Triemstra, Sato, le Wood, mochine oa khatiso). Ka mokhoa o ts'oanang, liphuputso tsa likhoto tsa banna li bonts'a hore androgens ha e na phello maemong a DA a basel kapa ho susumetsoa ke amphetamine-DABirgner, Kindlundh-Hogberg, Nyberg, le Bergstrom, 2006; empa hape bona Clark, Lindenfeld, le Gibbons, 1996). Ntle le moo, testosterone e na le tšusumetso e nyane ho litekanyetso tsa lisele tsa Acb DA (Thiblin, Finn, Ross, le Stenfors, 1999). Ka bobeli, tlhaiso-leseling ena e fana ka maikutlo a hore leha matlafatso ea testosterone e ka fetola mosebetsi oa DA ho Acb, mekhoa e ka fapana le ea cocaine kapa tse ling tse matlafatsang. Ntlheng ena, tlhaiso-leseling ea morao-rao e bonts'a hore ho pepeseha ho sa foleng ho AAS ho ka fetola kutloelo-bohloko ho DA ka ho fetola metabolism ea DA (Kurling, Kankaanpaa, Ellermaa, Karila, le Seppala, 2005), maemo a li-receptor tsa DA (Kindlundh, Lindblom, Bergstrom, Wikberg, le Nyberg, 2001; Kindlundh, Lindblom, le Nyberg, 2003) kapa morekisi oa DA (Kindlundh, Bergstrom, Monazzam, Hallberg, Blomqvist, Langstrom, le Nyberg, 2002).

Nakong ea hona joale, lipontšo tse ikhethang tsa li-steroid, li-receptors le libaka tsa boko tsa ts'ebetso bakeng sa ntlafatso ea testosterone ha li tsejoe. Ho ipapisitsoe le lipatlisiso tsa morao-rao tsa li-hamsters tse tsoang laboratoring ea rona, litlamorao tse matlafatsang tsa testosterone li bonahala li kopantsoe ke li-androgens le estrogens (DiMeo le Wood, 2006). Hangata AAS e hlekefetsoang e kenyelletsa androgens tse peli tse aromatizable le tse sa aromatiki (Gallaway, 1997; WADA, 2006). Sena se bolela hore ka bobeli AR le ER li ka fetisa mohopolo oa steroidal bakeng sa moputso. Ho na le menyetla e eketsehileng ea hore ntlafatso ea testosterone e ka kopanngoa ka ho kopanngoa ha li-receptor tsa classical le tse seng genomic.

Melao e 'maloa ea bopaki e supa liketsong tsa li-receptor tse seng tsa genomic liphellong tse matlafatsang tsa AAS. Ntle le kabo e fokolang ea AR ho Acb le VTA, nako ea matlafatso ea androgen e potlakile (<30 min), mme ts'ebetso ea lipontšo ka AR ea khale e kanna ea se ke ea potlaka ka ho lekana bakeng sa matlafatso. Ka hona, ho leka karolo ea AR eo e seng ea genomic ho matlafatso ea AAS, re sebelisitse mekhoa e 'meli e tlatselletsang (Feie. 7). Teko e le 'ngoe (Sato, Johansen, Jordan, le Wood, 2006), re lumelletse likhoto tse nang le testicular feminization mutation (Tfm, bona makasine ena) ho itšireletsa dihydrotestosterone (DHT), androgen e sa amaneng. Phetoho ea Tfm e fokotsa haholo ho tlama ha ligand ho AR. Leha ho le joalo, likhoto tsa Tfm le banab'abo ba banna ba mofuta o hlaha ba iphelisa ka tekanyo e lekanang ea DHT. Sena se pheha khang bakeng sa litlamorao tse seng tsa genomic tsa DHT. Phuputsong e ileng ea latela, re entse qeto ea hore na li-hamsters tsa banna li ka itaola DHT ho ikopanya le bovine serum albin (BSA, Feie. 8, Sato le Wood, 2007). Li-conjugates tsa DHT-BSA li-membrane-impermeable; ka hona litlamorao tsa bona li lekanyelitsoe holim'a seleng ea sele. Hamsters e ikemetseng DHT, joalo ka ha ho bonts'itsoe pejana (DiMeo le Wood, 2006). Ba bonts'itse khetho e tšoanang ho li-conjugates tsa DHT-BSA, empa ba hloleha ho itaola BSA feela.

    

Feie. 7

Karolelano ea li-nosepokes nakong ea ho iphelisa ea dihydrotestosterone (DHT) ka mofuta oa hlaha (WT, ka ho le letšehali, n = 17) le litekanyetso tsa testicular feminization (Tfm) (ka ho le letona, n = 13). Li-Nosepokes tsa lesoba le sebetsang (tse amanang le infusion ea DHT) li bonts'oa e le lits'oants'o tse ntšo, ha li-nosepokes (Hape …)

    

Feie. 8

Metsi a sebetsang ka boeona a sebetsang a sebetsang le a sa sebetseng a Syrian Hamsters ho DHT, BSA, DHT e kopantsoeng le BSA ka molek'hule ea li-linker [DHT-3-carboxymethyloxime-BSA (DCB), DHT-17-Hemisuccinate-BSA (DHB)] joalo ka DHT e nang le li-limolek'hule tse ling (Hape …)

Lintlha tsena li supa karolo e bohareng ea li-AR tsa lisele ho matlafatso ea androgen. Hajoale, mofuta oa li-receptor tse joalo ha o tsejoe. Ho 'nile ha fanoa ka tlhahiso ea hore li-androjeni li ka sebetsa seleng ea sele ka ho tlama ho arara ea membrane AR (Thomas, Ho roala, Pang, Berg, Tubbs, Benninghoff, le Doughty, 2006, hape bona khatiso ena). Sena se kanna sa ba ka sebopeho sa mofuta o mong oa nyutlelie oa mofuta oa AR joalokaha ho tlalehiloe ho hippocampus (Sarkey et al. Makasineng ena). Ntle le moo, lithuto tsa pejana li boetse li hlalositse libaka tsa marang-rang tse nang le li-steroid ho li-system tse ling tsa neurotransmitter. Ka ho khetheha, lihormone tse fapaneng tsa li-steroid ho kenyelletsa AAS li ka fetola ka mokhoa o hlakileng sebopeho sa GABA-A (Henderson, 2007; Lambert, Belelli, Peden, Vardy, le Petros, 2003). Ka mokhoa o ts'oanang, li-neurotheroids tse sulfated li ka fetola tšebetso ea N-methyl-DTse ling tse latellanang li-receptor subtypes (Malayev, Gibbs, le Farb, 2002) li-receptors. Ena ke sebaka sa bohlokoa sa lipatlisiso tsa nako e tlang.

Hobaneng ho lokela ho ba le membrane AR? Joalokaha ho hlalositsoe pejana, ho na le kamano e haufi pakeng tsa secretion ea androgen le boits'oaro bo monate ba sechaba. Re ka hakanya hore keketseho ea secretion ea testosterone e latelang ho tlolelana kapa ho loana e sebeletsa ho matlafatsa boitšoaro. Haeba ho joalo, ho hlokahala hore ho be le kopanyo e potlakileng ea ho susumetsa (boitšoaro) le moputso (testosterone). Sena se ka fumaneha hamolemo ka ho tlama ho membrane AR. Ntlheng ena, e tla ba ho khahlisang ho tseba hore na ho ts'oara secretion ea androgen nakong ea ho ruruha ho fokotsa litlamorao tsa boitšoaro ba thobalano.

Summary

Mona re lekola bopaki ba hore androgens ke babuelli ba matla ba boitšoaro bo susumetsoang ke batho ba baholo, le ho feta, hore nako ea ho pepeseha ha androgen nakong ea mananeo a nts'etsopele le boits'epo ba ts'ebetso ea ts'ebetso ea ts'ebetso ea bongoaneng ha e le motho e moholo. Li-steroid tsa Anabolic li potlakela ho fetoha sethethefatsi se rateloang tlhekefetso sa bacha ba US. Le ha AAS e kanna ea se be le tšebeliso e ngata ea koae kapa cineine, re sa tsoa qala ho utloisisa monyetla oa ho matlafatsa le ho lemalla ha androgen. Haholo-holo, ha lipapali tsa bacha li ntse li tsoela pele ho ba tlholisano, ho na le khatello e eketsehileng ea ho ntlafatsa baatlelete ho sebelisa li-steroid, ho qala ka ba banyenyane. Mokhoa ona oa tšoenya ha ho shebana le bopaki bo bocha ba ho fetoha ha tlhaho ha methapo ea methapo ho tsa bocha lilemong tsa bocha.

Leha ho na le tlhokomeliso e eketsehileng ke sechaba le saense ea liphetoho tse tebileng tsa tlhaho tsa bongoana, boithuto ba liteko tsa thuto ea methapo ea kutlo ea bongoana bo haelloa. Mefuta ea liphoofolo ea tsoelo-pele ea bocha e hlokahala ho etsa lipatlisiso tsa hore na nako ea ho pepesetsoa hoa li-hormone nakong ea kholo e eketsa menyetla ea motho ea lefu la psychopathology le tšebeliso ea lithethefatsi, le hore na ke liphihlelo life tse fokotsang kapa li holisang litla-morao tsa boits'oaro nakong ea nako ea pubertal. Mohlala, lintlha tsa kahisano tse kang khatello ea lithaka li mpefatsa litlamorao tsa nako ea nako ea lijo bakeng sa tšebeliso ea lithethefatsi le joala (Biehl, Natsuaki, le Ge, 2007; Patton, Novy, Lee, le Hickok, 2004; Simons-Morton le Haynie, 2003; Wichstrom le Pedersen, 2001). Mefuta ea liphoofolo ea nako ea lipapatso e tla boela e tsebise boiteko ba lipatlisiso tsa batho, hape e ka lebisa ho kenelletseng ka mokhoa o atlehang kalafo nakong ea bohlankana.

lumela hore baa fokola

Mongolo o botlaaseng ba leqephe

References