Tasirin Androgens akan Kwakwalwa

Androgens kamar testosterone gabaɗaya ana kallon su cikin sauƙi azaman haifar da tashin hankali, son rai da halayen rashin zaman lafiya. Koyaya, androgens suna yin tasiri ga ɗabi'a ta hanya mai sarƙaƙiya wacce ta haɗa da haɓaka halaye masu fa'ida da rashin zaman lafiya, tare da yanayin ɗabi'a don haɓaka matsayin zamantakewa.¹. A cikin wani binciken gwajin mummunan tasirin testosterone akan halayya, ƙungiyar testosterone ta kasance mai yuwuwa ta ba da lada mai kyau da aka samu a cikin gwaji yayin da kuma ta kasance mai tsauri wajen hukunta abubuwan da ake gani mara kyau.¹. Bugu da ƙari kuma, ba a sani ba shine cewa akwai shaidar da za ta ba da shawarar rage yawan androgens na serum kamar yadda aka gani a cikin ci gaban shekaru shine babban haɗari ga cututtuka na neurodegenerative, da kuma cewa tasirin ε4 na bambance-bambancen kwayoyin ApoE a cikin mice (wanda ke rage ƙwaƙwalwar ajiya da koyo na sararin samaniya). An hana shi ta hanyar gudanar da androgens².

Androgens su ne hormones na steroid wanda ke damun mai karɓar isrogen na nukiliya kuma yana haifar da rubutun kwayoyin halitta wanda ke haifar da ci gaban halayen jima'i na maza.³. Androgens an kafa endogenously ta hanyar steroidogenesis wanda shine tsarin matakai da yawa yana canza cholesterol zuwa hormones na steroid daban-daban.⁴. Sanannen hormones na steroid na endogenous tare da gagarumin tashin hankali na mai karɓar androgen shine testosterone da metabolite dihydrotestosterone.³. Sauran androgens na endogenous ana daukar su agonists masu rauni kuma galibi suna gabatowa ga steroidogenesis na testosterone. Testosterone wani abu ne na enzyme na aromatase, sabanin dihydrotestosterone wanda aka dauke shi a matsayin "tsarki" androgen, ta hanyar abin da aka daidaita shi zuwa isrogen estradiol mai karfi.⁵, Don haka wannan labarin zai yi ƙoƙari ya bambanta tasirin androgenic akan mammalian kwakwalwa daga siginar estrogenic kai tsaye daga metabolism na testosterone.

An san Estradiol yana da tasirin neuroprotective kuma ana bincikarsa azaman jiyya don AlzheimerCutar, amma kuma an ƙaddara cewa siginar androgenic na androgens a cikin ƙididdigar ilimin lissafi (ba tare da metabolism ba zuwa estrogens) shima neuroprotective ne.⁶. Sakamakon apoptotic da aka haifar a cikin al'adar neurones na ɗan adam yana raguwa lokacin da aka haɗa shi tare da testosterone da mai hana aromatase, da kuma lokacin da aka haɗa tare da androgen mibolerone maras aromatizable.⁶, bayar da shawarar metabolism na testosterone zuwa estradiol ba lallai ba ne don tasirin neuroprotective. Bugu da ƙari kuma, lokacin da aka haɗa testosterone tare da antiandrogen (flutamide), ba ta da tasirin kariya akan ƙwayoyin jikin mutum.⁶ ba da shawara siginar androgenic na iya zama neuroprotective.

Gudanar da babban kashi (5mg / kg daidai da 400mg a cikin mutum na 80kg) androgens (ciki har da testosterone propionate da ester dihydrotestosterone wanda ba a bayyana ba) a cikin berayen yana rage dopamine a cikin hypothalamus da amygdala, ba tare da rinjayar norepinephrine da serotonin ba, kuma ba tare da wani tasiri ba. akan sauran kwakwalwa yankuna⁷. Bugu da ƙari kuma, androgens suna rinjayar hali ta hanyar rinjayar tsarin mesocorticolimbic⁸. Tsarin mesocorticolimbic yana da tasiri a cikin lada koyo (saboda haka jaraba), don haka yana tasiri halaye⁹.

Gudanar da Iltesterone a cikin Ayyukan Komawa da berayen da ke haifar da kwandishan wurin saboda samun lada tare da lada (kwatankwacin, wannan shima sakamako ne na sakin kwayoyi na Dopamine)⁸. An kawar da wannan amsa ga androgens lokacin da dopamine D₁ da kuma D₂ receptor antagonist ne tare da gudanarwa⁸, yana nuna tasirin testosterone akan siginar dopamine. Matasan kajin maza suna gudanar da ƙwayar ƙwayar ƙwayar cuta ta testosterone masu launi da aka saba kuma suna da ƙarin ma'aurata da ke neman dagewa ba kamar kajin da aka yi wa placebo ba wanda ya nuna ƙarin sassauci a cikin ɗabi'a.⁸. Testosterone yana da alama yana hana ikon canza dabarun mayar da martani lokacin da ba shi da tasiri, yana goyan bayan dagewar-rage tasirin maganin antiandrogen a cikin kajin.⁸.

Berayen gonadectomised ba su da juriya a cikin ayyukan kwantar da tarzoma kuma sun nuna gazawa a cikin ƙwaƙwalwar aiki idan aka kwatanta da berayen gonadectomised na testosterone.⁸. Bugu da ƙari kuma, rage girman ƙwaƙƙwaran mai karɓar mai karɓar androgen kamar ta hanyar antiandrogens yana haifar da raguwa a cikin ayyukan zartarwa, kulawar fahimi, hankali da ikon gani, tare da raguwa a lokaci guda a cikin launin toka a cikin sassan prefrontal cortex.⁸. Dendritic spine density yana karuwa a cikin tsarin limbic na berayen da aka bi da su tare da manyan allurai na testosterone. A cikin tsaka-tsakin prefrontal cortex, dihydrotestosterone yana haɓaka samuwar kashin baya na dendritic⁸, yana nuna mahimmanci ga androgens a cikin kwakwalwa.

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References:

1. Dreher J., Dunne S., et al 2016. Testosterone yana haifar da halayen pro- da rashin zaman lafiya Abubuwan da aka yi na Cibiyar Kimiyya ta Kasa (PNAS) Oct 2016, 113 (41) 11633-11638; DOI: https://doi.org/10.1073/pnas.1608085113  

2. Jordan, CL, & Doncarlos, L. (2008). Androgens a cikin kiwon lafiya da cututtuka: wani bayyani. Hormones da hali, 53(5), 589-595. DOI: https://doi.org/10.1016/j.yhbeh.2008.02.016  

3. Handelsman DJ. Androgen Physiology, Pharmacology, Amfani da rashin amfani. [An sabunta 2020 Oktoba 5]. A cikin: Feingold KR, Anawalt B, Boyce A, et al., masu gyara. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Akwai daga: https://www.ncbi.nlm.nih.gov/books/NBK279000/  

4. Encyclopedia na Neuroscience, 2009. Steroidogenesis. Akwai akan layi a https://www.sciencedirect.com/topics/medicine-and-dentistry/steroidogenesis 

5. Maganar Magungunan Masu Siyar da Kyauta, 2016. Aromatase. Akwai akan layi a https://www.sciencedirect.com/topics/chemistry/aromatase 

6. Hammond J, Le Q, Goodyer C, Gelfand M, Trifiro M, LeBlanc A. Testosterone-tsakanin neuroprotection ta hanyar mai karɓa na androgen a cikin ƙananan ƙananan ƙananan mutane. J Neurochem. 2001 Juni; 77 (5): 1319-26. PMID: 11389183. DOI: https://doi.org/10.1046/j.1471-4159.2001.00345.x  

7. Vermes I, Várszegi M, Tóth EK, Telegdy G. Action na androgenic steroids a kan kwakwalwa neurotransmitters a cikin berayen. Neuroendocrinology. 1979;28 (6): 386-93. DOI: https://doi.org/10.1159/000122887  

8. Tobiansky D., Wallin-Miller K., et al 2018. Tsarin Androgen na Tsarin Mesocorticolimbic da Ayyukan Gudanarwa. Gaba. Endocrinol., 05 Yuni 2018. DOI: https://doi.org/10.3389/fendo.2018.00279  

9. Hukumar Tarayyar Turai 2019. CORDIS EU Sakamakon Binciken Bincike - Tsarin Mesocorticolimbic: Tsarin Aiki na Aiki, Plasticity-Evoked Synaptic Plasticity & Halayyar Halayyar Haɗin Synaptic. Akwai akan layi a https://cordis.europa.eu/project/id/322541 

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