Androgens e bapala Karolo ea Bohlokoa ho Boloka Architeme le Tloaelo ea Penile: Tlhahlobo
TLHOKOMELENG M. TS'ELISO
Ho tsoa Lefapheng la Biochemistry and Urology, Boston University School of Medicine, Boston, Massachusetts.
| Litaba tse mabapi le: Ngaka Abdulmaged M. Traish, Moprofesa oa Biochemistry le Urology, Motsamaisi, Laboratories bakeng sa Bongaka ba Thobalano, Setsi sa Bongaka ba Thobalano, Boston University School of Medicine, Setsi sa Patlisiso ea Advanced Biomedical, 700 Albany St, W607, Boston, MA 02118 ( lengolo-tsoibila: [imeile e sirelelitsoe]). |
| E amohetse phatlalatso ea June 13, 2008; e amohetse ho phatlalatsoa ka September 17, 2008. |
inahaneloang
Androgens ke ea bohlokoa bakeng sa nts'etsopele, kholo, le ho lokisa sebopeho sa penile, le ho laola physology ea erectile ka li-multiplemechanisms. Mona re fana ka kakaretso e akaretsang ea lipatlisiso tsa mantlha tsa bokhabane tse amanang le androgen modulation ea erectiletissue architecture le physiology. Sehlopha se seng sa lipaki tse bonts'ang karolo e bohlokoa ea li-androgens ho erectilephysiology. Boithuto ba meetso ea liphoofolo bo fane ka tsebo ea mantlha mabapi le karolo ea androgens ho fetoheng meaho ea meralo ea methapo, limolek'hule le boikoetliso ba 'mele. Boitsebiso bo thehiloeng tsebong bo hlahileng ka laboratoring ea rona le bo tlalehiloeng ke ba bang, webelise hore androgens ba bapala karolo ea bohlokoa ho boloka sebopeho le ts'ebetso ea marang-rang a methapo ea methapo ea kutlo, botšepehi ba Corpora cavernosa, tunicaalbuginea, le endothelium ea libaka tse bulehileng. Ho feta moo, androgens e bapala karolo ea bohlokoa ho tataiseng lisele tsa phapang ea mantlha hore e be mesifa e boreleli ea trabecular. Thutong ena, re tla tsepamisa mohopolo oa rona mabapi le liphumano tse amanang le therole ea androgens mabapi le taolo ea meaho ea methapo ea methapo ho hlophisa mosebetsi oa penile. Tsebo ena e na le tšusumetso e matla tšebelisong ea monyetla ea ts'ebeliso ea li-androgens ho tsa bongaka ho phekola bakuli ba nang le bothata ba ho se sebetse ka mokokotlo.
Mantsoe a bohlokoa: Andropause, ho senyeha ha erectile, hormone, penis, adipogenesis, le androgen, corpus cavernosum, ho se sebetse ka thobalano, mesifa e boreleli
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Corporeal veno-occlusive dysfunction ke sesosa sa bohlokoa sa ho se sebetse hantle ha erectile dysfunction mme e tšoauoa ka tlhokeho e nyolohang ea phallo ea phallo ho boloka erection nakong ea kolechevaluation ea erection ka intracavernous saline infusion (Hatzichristouet al, 1995, 1999; Nehra et al, 1996, 1998; Udelson et al, 1998; Mulhall et al, 2004). Corporeal veno-occlusive dysfunctionalone kapa e kopantsoe le lefu la ramatiki ke hemodynamicabnormality e ikhethileng e bakang ho hloka karabelo ho intecacavernous pharmacotherapy (Rajfer et al, 1988; Mulhall et al, 1997; Aversa et al, 2003;Wespes et al, 2005; Hwang et al, 2006). Ho ba teng ha lefu la mesifa le khokahano ea sincomitantaros le etsa hore ho be thata ho tseba le ho li phekola.
Leha boiteko bo entsoe ke li-laboriesiesto tse 'maloa tse hlalosang le ho utloisisa karolo ea li-androgens ho laola motheo oa sele le molek'hule ka mosebetsi oa erectile le someprogress e se e entsoe, likheo tse' maloa li sala. Tsena li kenyelletsa karolo ea li-androgens tšebetsong ea botsitso le tšebetso tšebetsong ea methapo le methapo ea methapo, kholo le ho sebetsa ha mesifa e boreleli, le tšebetso ea endothelium andmaintiment ea methapo ea methapo ea methapo le attenuationof fibrosis. Mona re hlahisa mofuta o sebetsang oa androgen Actionin erectile function (Setšoantšo sa 2). U sebelisa sebopeho sena, wediscuss karolo ea androgens likarolong tsa methapo ea methapo e kenyelletsang 1) methapo ea methapo, 2) mesifa ea trabecular boreleli, 3) phapang ea lisele tsa methapo ea methapo ea methapo, le 4) vascular endothelium, le 5) vasica albuginea andconn.
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Androgens e fetola sebopeho le tšebetso ea pelvic ganglia (Meusburger le Hloko, 2001; Keast et al, 2002). Giuliano et al (2004) o khothalelitse hore androgens e fetole ts'ebetso ea erectile e sebetsang ho li-neuron tsa postganglionic parasympathetic. Armaganet al (2007) e bonts'itse ho hloka taolo ea androgen ka ho lahla sebopeho sa methapo ea methapo. Tlhatlhobo ena e lumellana le e entsoeng ke Ntate et al (2000a,b) moo phatlalatso e ileng ea fokotsa lits'enyehelo tsa NADPH ka hara thipa le dorsalnerves le kalafo ea testosterone tsa khutlisetsa maemo ana a taolo ea methapo ea methapo. Roger et al (2003) hape e bontšitse hore phatlalatso e fetotse sebopeho sa methapo ea methapo 'me ea baka ho lutla ho matla. Phekolo ea testosterone hang kamora ho fallisoa e ile ea thibela ho lutla ha venous le ho khutlisetsa intracavernosalpressure ho boleng bo ts'oanang le ba liphoofolo tse matla. Ka ho khahlisang, kalafo ea liphoofolo tse ferekaneng tse nang le vascular endothelial growfactor (VEGF) e khutliselitse sebopeho sa methapo le ts'ebetso ea veno-occlusive.Because androgens e bontšitsoe ho laola polelo ea VEGF (Haggestrom et al, 1999), ho ka etsahala hore VEGF synt syntinin ea corpus cavernosum e laoloa ka tlase ho kalafo ea liphoofolo le liteko tsa testosterone e etsa hore ho be le mofuta oa VEGF, ka hona, ho ba le litlamorao tse amanang le androgen ho Corpus cavernosum.
Orchiectomy e hlahisitse phokotso e kholo ho intracavernosalpressure e hlahisitsoeng ke tšusumetso ea tšimo ea motlakase ea pelvicnerve. Sena se ile sa khutlisoa ke phetiso ea testosterone, ho fana ka maikutlo a hore testosterone e bapala karolo ea bohlokoa khokahanong ea marang-rang ea taolo ea penile erection (Simpson le Marshal, 1908; Müller et al, 1988; Heaton le Varrin, 1994; Mill et al, 1994; Bivalacqua et al, 1998; Traish et al, 1999; Palese et al, 2003; Suzuki et al, 2007). Ho ekelletsa moo, Suzuki et al (2007) bontšthat, ho fapana le likarabo tsa erectile tse hlahisitsoeng ke motlakase oa motlakase oa methapo ea methapo, e ileng ea fokotsoa empa e sa felisoe ka liphoofolo tse lahliloeng, karabelo ea erectile ka ho ts'oaroa hoa motlakase ka mokhoa oa "medial preoptic areawere" e tlosoa kamora ho fetisoa ebe e khutlisoa ka botlalo testosterone.
Androgens Boloka Karolo ea 'Mino oa Phula ea Peile Trabecular Smooth le Ts'ebetso
Ho na le bopaki bo hlakileng bo bontšang hore mesifa ea penile trabecularsmooth e bapala karolo ea bohlokoa ho laoleng qoqothong (Saenz de Tejada, 2002). Sebopeho se nepahetseng sa liphetoho tse amanang le tsona le sebopeho tse etsahalang ka har'a boreleli kamora ho haelloa ke androgen, leha ho le joalo, ha li tsejoe.
Tlholo ea Androgen mehlaleng ea liphoofolo, ka ho buoa kapa ho phatlalatsoa ka bongaka, e hlahisitse phokotso ea bohlokoa liteng tsa trabecular boremuscle, le keketseho e nyane ea extracellular connectivetissue matrix (Traish et al, 1999). Phetoho ena sebopeho sa mesifa ea maoto e amana le phokotso ea khatello ea methapo ea methapo e le ho arabela tsusumetso ea methapo ea kutlo (Simpson le Marshal, 1908; Müller et al, 1988; Takahashi et al, 1991; Heaton le Varrin, 1994; Mill et al, 1994; Bivalacqua et al, 1998; Traish et al,1999, 2003; Palese et al, 2003; Suzuki et al, 2007). Ntle le moo, lithuto tsa maqhubu a lithane tse tsoang liphoofolong tse tsoang liphoofolong tse fumanehang li sa hlophiseha, li le ngata haholo tsa li-vactos tsa cytoplasmic le lipalo tse fokotsang tsa cytoplasmic myofilaments (Persson et al, 1989; Traish and Kim, 2005;Traish and Guay, 2006; Traish et al, 2007). Tahlehelo ea boreleli bo bakoang ke ho haelloa ke androgen ho boleloa hore ke keketseho ea lefu le hlophisitsoeng la seleng, sethopo se fumanehang, le phapang ea adipocyte ho tsoa liseleng tse tlang pele ho nako (Shabsigh et al, 1998; Traish et al, 2005). Liphetoho tse ling tse hlokomelehang ho likarolo tsa penile tisuestructural tse tlalehiloeng ho bakuli ba nang le erectile dysfunctionwere borerang atrophy le ho bokellana ha extracellularmatrix, e kenyelletsoeng haholo ke collagen fibrils.
Motsoako o boreleli oa cosora cavernosa o amanang le lisele tse sebetsanang, o lekantsoeng le nalane e ikhethang, o hlalosoa e le mesifa e boreleli ho ea hlahang tisueratio. Ho fokotseha ha litaba tsa mesifa ea borena ea "trabecular boreleli" ho lebelletsoe ho hlahisa matšoao a mesifa 'me qetellong ho se sebetse hantle ha matšoao a amanang le bongaka le litheko tsa bongaka ho banna ba nang le erectiledysfunction li ne li amana le litaba tsa "tis" tsa "mesoralsmooth" tsa mesifa (Nehra et al, 1996, 1998; Wespes et al, 1997, 1998). Liseleng tse tsoang ho banna ba nang le ED, mesifa e boreleli e bontšitsoeng morphology e nang le li-sparse glycogen particlesand e kopantsoeng mitochondria e fumanoang liseleng tsohle. Mookotaba o bonts'itseng sebopeho sa "pleomorphic" mme li-cell cell cellwere li ile tsa fokotseha kapa tsa felisoa. Lithuto tsena li khothalelitse hore dikahare tsa collagen tse ntlafalitsoeng (mohlala, li-connective tiske) li lumellane le ho theoha ha methapo ea methapo ea methapo ea methapo ea methapo, ho fokotsa ts'ebetso, 'me ho felle ka phallo ea mali a penile, ho hlahisa ho se sebetse hantle ha erectile (Persson et al, 1989; Mersdorf et al, 1991).
Androgens E laola Phapang ea Lisele tsa Pluripotent Precursor Ho ea Trabecular Smooth Muscle
Ho haelloa ke Androgen mohlaleng oa phoofolo ho felletse ka hore ho bokellane li-adipocytes liseleng tsa penile, haholo-holo subtunicalregion (Traish et al, 2005). Testosterone e khutlisetsang ponahalo ea nalane ea cavernosal e nchafalitsoeng. The tisalterations tse bonoang li ne li amana le ho hlohlelletsa khatello ea methapo ea kutlo. Rona le ba bang re hlokometse ho bokella ha adipocytes ka lipakete tsa penile tsa diabetesicanimals (Traish le Kim 2005; Kovanecz et al, 2006). Hobane lefu la tsoekere le amahanngoa le phallo ea androgen e fokotsehileng, ho ka etsahala hore ho bokelloa ha li-adipocytes joalo ka lebaka la tahlehelo ea taolo ea androgen ea phapang ea sele. Ka mokhoa o ts'oanang, kalafo ea liphoofolo tse tona tse nang le bisphenol A, e tsebahalang hore e na le ts'ebetso ea estrogenic, le eona e felletse ka ho bokella ha adipocytes ho Corpora cavernosa (Khoeli le al, 2001, 2004). Sena se fana ka maikutlo a hore li-estrogens li ka 'na tsa loants'oa androgen Actionin the corpus cavernosum' me tsa baka phapang ea lisele tsa precursorpluripotent ho adipocytes. Ka botšepehi et al (2005a,b; 2007a,b) li bonts'itse ka mokhoa o hlakileng hore kalafo ea liphoofolo tse nang le matsatsi a 2 e tsoetseng pele e bakile ho fokotsoa ha litekanyetso tsa testosterone le ho bokellana ha adipocytes ka har'a li-Corpora cavernosa tsa phoofolo e butsoitseng. Bhasin et al (2003) o khothalelitse hore androgens e laole phapang ea lisele tse maqhubu a mangata hore e be phapanyetsano ea mesifa e boreleli ho isa ho li-adipocytes. Hypothesiswas ena e tšehelitsoe hape ke liphetho tsa Singh et al (2003, 2006), ea bonts'itseng phapang ea li-pluripotentcells ho mesifa e boreleli le thibelo ea adipogenesis li itšetlehileng ka androgen. Re hatisitse hore ho bokellana ha adipocytesin khokahano lipakeng tsa tunica albuginea le 'mele ea cavernosal ho ka kenya letsoho ho se sebetseng hantle ha khoebo.
Androgens Boloka Karolo ea Vascular Endothelial le Ts'ebetso
Ho thehiloe ka nepo hore vascular endothelium modulatescorpus cavernosum mesifa e boreleli ea molumo ka tlhahiso ea lintho tsa NO andparacrine, joalo ka li-prostaglandins, endothelin, ntlha ea methapo ea methapo, le phetoho ea kholo ea β1 [TGF-β1] (Moreland, 2000; Bivalacqua et al, 2003, 2005; Solomon et al, 2003; Guay 2005, 2007; Musicki le Burnett, 2007; Watts et al, 2007) Ho rohakoa ho hoholo ka endothelium (ke hore, ischemia, hypoxia, le arteriosulinosis) ho ka hlahisa tlhahiso e eketsehang kapa e fokotsehileng ea lintlha tsa paracrine, tse fetolang ts'ebetso le lisele tsa "mesifa"Moreland, 2000). Phuputso ea morao-rao keLu et al (2007) e bonts'itse ho hloka taolo ea androgen ke castrationor 5
kalafo ea -ductase inhibitor e hlahisitse tšenyo ho sebopeho sa endotheliumstat, joalo ka ha ho khethiloe ke microscopy ea elektrone. Liphoofolo tse haufi tsa endotheliumfrom li bontšitse libaka tse boreleli tse nang le likarolo tse fapaneng tsa sebopeho. Endothelium e tsoang liphoofolong tse phoqotsoeng tsa liphoofolo tse koahelang limela le tse hlahang ka bongata, 'me ea bonahala e sa khahlise. Mabitso a selefounu a sele a ile a fetoloa mme ho khokhotheloa hoa likhase tse khubelu tsa mali ho fihla holim'a endothelium. Administrationof testosterone ho liphoofolo tse fallisitsoeng ka tsela e itseng e khutliselitsoeng holima botsitso, tse nang le liso tse 'maloa tse setseng tse lemohuang. Tsebiso e tsoang thutong ena e bontšitse hore ts'oaetso ea androgen deficiencyproduces vascular endothelial le hore endothelial merativeinteity e khutlisoa ke tsamaiso ea androgen. Akishitaet al (2007) e tlaleha hore, ho 187 e 'ngoe ea li-outpatientsw tse ling tse latellanang tsa banna ba hlahang ka nako e telele ea li-vasodilation (FMD) tsa mokokotlo oa mokokotlo o sebelisang ultrasonography, kakaretso le freetestosterone li ne li hokahane haholo le liperesente tsa FMD. Tlhabollo ena e ne e ikemetse ka lilemo, index ea boima ba 'mele, khatello ea mali, hyperlipidemia, lefu la tsoekere, le ho tsuba, ho fana ka maikutlo a tšireletso a testosterone ea mehleng ho endothelium.
Ho khutlisoa kapa ho nchafatsoa ha kotsi ea endothelial ho latela, ho ipapisitse le letamo la lisele tsa progenitor tse tlang pele ho nako le lisele tse kholo tse potolohang tsa prootitoral (EPCs) .Foresta et al (2006, 2008) e fuputse litlamorao tsa kalafo ea nako e telele ho banna ba nang le li-PC le li-EPC tsa hypogonadotropic hypogonadismon. Bangoli ba khothalelitse hore bakuli ba nang le "hypogonadal Patihad" ba fokotse maemo a li-PC le li-EPC le hore testosterone e kopane le keketseho e kholo ea lisele tsena. Sengoli se ile sa qolla hore hypogonadism e amahanngoa le li-PC le li-EPC tse fokotsang palo. Keketseho ea kholo ea tšebetso, phetohelo, le ts'ebetso ea kolone ea li-EPC tse susumetsoang ke androgens ke tsela e arolelanoang ka mokhoa oa AR (Foresta et al, 2008).
Re fana ka tlhahiso ea hore khaello ea androgen - e bakang likotsi tsa toendothelial lisele tse holisang bethe ea vassa ea penis extasessynthesis le tokollo ea TGF-β1, endothelin, le contractileprostanoids, empa e fokotsa NO. Liphetho tsa biologicalinsults joalo ho endothelium li ne li tla tlisa liphetoho phetohong ea mokokotlo oa messoth, e lebisang ho extracellularmatrix deposition (fibrosis), cell atrophy, le kholo ea lisele tsa inhibitionof (hypoplasia). Fibrosis, ka hona, e ka kenya letsoho ho fetoha ha konteraka le ho fokotsa ho latela (joalo ka qeto), ho lebisang ho se sebetseng ha vasculogenic erectile.
Androgens E Boloke Bothata ba Stika ba Tunica Albuginea le Lits'ebetso tsa Khokahano ea Tissue Matrix Fibroelastic
Shen et al (2003) e bonts'itse, liphoofolong tse lahliloeng, tlatsetso e kholo boteng ba tunica albuginea ha e bapisoa le liphoofolo tse hlakileng. Ho liphoofolo tse sa tsitsang, mofuta oa tunica ke likhoele tse boreleli, 'me boqapi ba masela a joalo a ile a bonts'a litokisetso tsa kamehla. Ka lehlakoreng le leng, liphoofolo tsa "tunica albugineafrom castrate" li bontsitse ho fokola ha mesifa ea elastic fiber le ho khutlisetsa likhoele tsena ka collagen. Bangoli ba fumane hore androgens ke tsa bohlokoa bakeng sa ho lokisa sebopeho se tloaelehileng sa penile tunica albuginea.
Androgen tlatsetso ka ho fetisoa hoa mefuta ea liphoofolo e hlahisitse keketseho e kholo ho matrix a kantle ho kantle, ka mokhoa o kopaneng oa mesifa e boreleli ho kenyelletsa tekanyo ea litho tsa 'mele ka hoo e ka bang2-fold.Takahashi et al, 1991; Traish et al, 1999, 2003) .Le phokotso ea thepa ea "fiber" e fokotsang litheko tsa methapo ea methapo le ho fihlela penile hemodynamics, e bakang ho senyeha ha erectile (Wespes et al, 1990, 1991; Jevtich, 1991; Nehra et al, 1996). Boithuto bo 'maloa bo khothalelitse hore androgens e fetole matrix a tsoang kantle ho lintlafatso ka lintlha tsa kholo ea polelo (Natoli et al, 2005). Sena, leha ho le joalo, se lokela ho hlahlojoa ka ho eketsehileng lithong tsa penile. Ho fokotseha ha likhoele tse phahameng le liphetoho mekhoeng ea microscopic ho ka baka ho se sebetse hantle ha kelello ka ho sitisa ts'ebetso ea venoocclusive ea tunica albuginea (Moditjhaba et al, 1996; Akkus et al, 1997). Lithuto tsa morao-rao li netefalitse ho khutlisetsa tšebetsong ho banna ba nang le bothata ba ho se sebetse hantle ha erectile ka lebaka la kalafo ea androgen (Yassin et al, 2006; Kurbatov et al, 2008a,b). Maikutlo ana a fana ka maikutlo a hore androgensplay e bapala karolo ea ho boloka meralo ea lithane tsa erectile.
Kakaretso le Liphello
Ho na le bopaki bo bongata bo fanang ka bopaki ba hore androgensregates sebopeho le tšebetso ea methapo ea penile, vascularendothelium, mesifa e boreleli ea trabecular, matrix ea tishu e kopanetsoeng le tunica albuginea. Ho feta moo, androgens e laola lisele tse khethollang likarolo tsa 'mele ho fetoha mesifa e boreleli ea trabecular le inhibitdifferentiation ho adipocytes. Ho batho, khaello ea androgen e iponahatsa ka har'a li-pathologies tsa kliniki, joalo ka 1) nts'etsopele e sa lekanang ea botona le 2) tahlehelo ea tšebetso ea erectile ka kankere ea lefu la senya kapa benign Prostatic hyperplasiamanaged ka bongaka kapa ts'ebetso ea bongaka kapa li-antiandrogentherapy. Tlatsetso ea Androgen ho bakuli ba hypogonadal e ntlafatsa ts'ebetso. Tlhahlobo ena ea bongaka, hammoho le tlhaiso-leseling ea tlhahlobo ea peleho, e fana ka maikutlo a hore testosterone e khutlisetsa likarolo tsa sebopeho le ho ntlafatsa penile hemodynamics.
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Ka kakaretso, androgens e bapala karolo ea bohlokoa ho boloka meralo ea erectiletissue (Setšoantšo sa 3), le erectile physiology ka ho hlophisa mosebetsi oa penile neural le ho hlophisoa ha 'mele ha mesifa e boreleli, endothelium, le matrix ea tiske e kopanyang, hammoho le lits'oaetso tsa metabolic le li-signature.
lumela hore baa fokola
Mongolo oa sehlooho
Pampiri ena e ipapisitse le nehelano Sebokeng se Ikhethileng sa la 12 Mmesa 2008, "Mekhoa ea Phekolo ea Bophelo bo Botle ba Basali ba Ho Kopanela Liphate le Hormonal," e amanang le Seboka sa Selemo le Selemo sa American Societyof Andrology, eo moemeli ea fanang ka eona a fumaneng setsi sa tlhompho.
Ngaka Traish o na le likamano tsa boeletsi le / kapa tsa lichelete leBayer AG.
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