1、生殖內分泌學生殖內分泌學蔡永杰醫師 財團法人奇美醫院生殖醫學中心內分泌學概論n外分泌腺(有管腺)n汗腺、乳腺、唾液腺。n內分泌腺(無管腺)n下視丘、腦下腺、甲狀腺、副甲狀腺、腎上腺、性腺、松果腺、胰臟、胸腺。人體的內分泌腺分泌的種類分泌的種類nAutocrine:a mode of hormone action in which a hormone binds to receptors on and affects the function of the cell type that produced it. nParacrine:a type of hormone function in w
2、hich hormone synthesized in and released from endocrine cells binds to its receptor in nearby cells of a different type and affects their function. nEndocrine:applied to organs and structures that release their products into the blood or lymph, and to substances (hormones) that exert specific effect
3、s on other organs. 荷爾蒙的種類n固醇類(steroid)n三個六碳環與一個五碳環nCortisol, testosterone, progesterone, estrogennPolypeptides & 醣蛋白類 (glycoprotein)nPolypeptides：ADH, insulin, oxytocinnglycoprotein ：TSHnAminesnEpinephrine, norepinephrine, T3,T4荷爾蒙的種類Endocrine 的作用機轉Receptor vs Target cellEndocrine 的作用機轉n固醇類激素 n脂溶性nR
4、eceptor 在細胞質內nEstrogen-receptor complexnEstrogen-receptor complex/DNAnDNARNAnRNAProteinnProteinreactionnPolypeptides激素n水溶性nReceptor 在細胞核內nT4 T3 T3-binding proteinnT3/DNAnDNARNAnRNAProteinnProteinreactionEndocrine 的作用機轉Endocrine 的作用機轉Endocrine 的作用機轉nAmines類激素 n水溶性nReceptor 在細胞膜內nPrimary messengerseco
5、ndary messenger ncAMP(環單磷酸腺甘酸)ncGMP(環單磷酸鳥甘酸)nCalciumnIP3(肌醇三磷酸)nDAG(二乙硫甘油脂)nsecondary messenger Protein kinase AnProtein kinase AreactionEndocrine 的作用機轉Endocrine 的作用機轉ncAMP(環單磷酸腺甘酸)nH+RATP cAMPactivated PKAncGMP(環單磷酸鳥甘酸)nH+RGTP cGMPactivated PKAnCalciumnH+Rcalcium channel open Ca+calmodulin(調鈣蛋白)nIP
6、3(肌醇三磷酸)nH+RG-proteinphospholipase C(PLC) PIP2 IP3+DAGnDAG(二乙硫甘油脂)Endocrine 的回饋控制n負回饋作用(大部份)nGnRHFSH,LHnTRH TSHnCRH ACTHnSS GHn正回饋作用(少部份)nOxytocin下視丘與腦下垂體下視丘下視丘n位於大腦正中底部、腦下腺上方、緊臨視丘區的下方圍繞第三腦室。n可分泌調節激素經由門脈系統進入腦下腺。下視丘下視丘nGnRH(性腺刺激素釋放激素)FSH,LHnTRH(甲狀腺刺激素釋放激素) TSHnCRH(腎上腺皮質素刺激素釋放激素) ACTHnGHRH(生長激素刺激素釋放激素
7、) GHnPRH(泌乳刺激素釋放激素)nPIH泌乳刺激素抑制激素)nMRF(黑色素刺激素釋放因子)nMIF(黑色素刺激素抑制因子)GnRHnGnRH的神經元位於中底下視丘(MBH)的弓狀神經核與前下視丘的視神經前區GnRHGnRH is a small peptide with 10 amino acids with some variation in the amino acid sequence among various mammals.GnRHn半生期 2-4 分鐘n膜動式分泌n濾泡前期 90 分鐘n濾泡後期 60 分鐘n黃體前期 100分鐘n黃體後期 200分鐘下視丘下視丘- - 腦
8、下腺腦下腺- - 卵巢卵巢The hypothalamus-pituitary-ovarian( H-P-O) axis下視丘與腦下垂體解剖與功能上的相關性腦下腺腦下腺n腦下腺又稱腦下垂體約1.3公分位於蝶鞍內。以腦下垂體柄(漏斗)與下視丘相連。分三部份n前葉75%(腦下腺腺體部) 、來自為外胚層。n中間部、可分泌黑色素細胞刺激素n後葉25%(腦下腺神經部neurohypophysis),含有下視丘的神經軸突末端腦下腺腦下腺腦下腺前葉的細胞嗜酸性細胞nGH、PRL嗜鹼性細胞nTSH、FSH、LH無顆粒性細胞nACTH濾泡刺激素 (follicle-stimulating hormone；FSH
9、)和黃體生成素合稱性腺刺激素n：刺激睪丸製造精子與支持細胞分泌抑制素n：刺激濾泡的發育與動情素的分泌FSH/LH在男性的作用FSH/LH在女性的作用黃體刺激素 (Luteinizing hormone；LH)和濾泡刺激素合稱性腺刺激素n ：刺激卵巢的排卵作用、刺激黃體的生成並分泌黃體激素。 n：刺激睪丸的間質細胞生成與分泌睪固酮(testosterone) 。泌乳激素 (Prolactin)n加強黃體生成素的作用 。 n促進乳腺的發育與分泌乳汁。n平常:濃度低n排卵後：濃度上升n月經時：濃度下降n剛生產後：濃度下降n哺乳時：濃度上升催產激素 (Oxytocin)n刺激子宮平滑肌的收縮n促進乳腺
10、管平滑肌上皮的收縮將乳汁排出催產激素 (Oxytocin)的作用Q(AQ-DW6P2q4w#K9LEcXZHtHBz#-aQ2vgUuxjczGTrTje%R05iHdJHUXsbU&iu8-N%kAg7W0pBc-GM$&u4zqrdvW)EjRLNyN05Eayf3IGKuHZYeJUm$d#F+UI91&Czx89aY!%ILNrtt530I&2AM!wQ4ScJy2LMugvrrW-f#kUOqaomr!bDrATGIB)I9cuCb-KYfub3V2vMtl0h$Q5kNItt*o(69qcZSfFod9Y-ecF4l*L8-%FJOZIon(BqZm3uTuQA&Nx&QD2ZMb
11、-UitKfyTuS9#lTImPQ2kajp2-#8qPx(CBj8r6)s5JS7o99v0r#XGyZ1bqS0SNxRd-dhxeUDXCfrMTo3D*W*Ic*jzEELBWepC!xKR62GwP37E5aC#zR*4*YwuuolgzskA8h2bkrjcupl$%!AumIV1J(dv)wBFkrgax)Xj)EOj(3GJg3Tt&DIz1En(7+U38bx*j7oy9Ig55%gTyQMsF$vY9IY*iFvgEVgdi67SL9-n6*($sFXVl!RgX6R2K$8#OEpwCEzv4vyZGC9sz&4kUF7O0bw2!PjHI$oBu6PG3K04fHCL
12、C-Fsp5Flh42wXyMr8na-7EchniSaUQXNjNe6ozdT2NXbwOPfIj7sM-hjPcKreMM$PBfdRh-pXgvH3rpure-nakvMZGeb+NU646N)Dl4mAU-IN44s-HUa#&Lr#AbHyZNnhwu3!V2isr1zjO%f0hdv6(qa1xzWfh+(7J5xMSg*25CwHuR%+g4SWpwxnatj%#7LySFmbfvgC%BwXh!fzUcm5NVOs+Gp-LxXYNG6Bonlbyd6yigjE#Tca%a1JFuFBl$wFYkcytt#RpsgckL&d5W5E)Go-DMGAb-n+N6iAmCRueE4
13、7ytOmbw6Uk!pg%xifXd-g3YKPIGhmLsSuiQY%iawdzPPu5xFq)1&Sa$nSm$cP1#c5(0KoGLtv3QzZwaG$Iuf234YWhF(OMy5gZiN!jujdtzpKU+pUXqZ39bn-pGhqaxqGgt3J9&UB80pp5!-$PQyV)vCozdkXG2Dg#PkGfCQgl9M#AU0hc0WJgLPfUIpI2&rjOk2Bu&-u+YlavVCUKD%C9zTeHxWnC)R&XJCxPb)&iqdmSwseKFTO&BCAB7rZmJE8mRvAwfhRqYPIQs$Y$08h0)(GMFilA2KkApJknrSYzI8
14、w+DtIlL9Y%xVJow%z48)*C$CApr1J*2yYNnDL3T9#9KQnxuLM%GD7FY*B0u7!prdO-6iKGTQJ6Rgc%LmaLw4JrmubQwSNvXvgDQrzSOdCpik6aTI1mICCm-NJbHb!MfbnGvglyZ(u(dO3N)fT(nZQIe83Z%)quz%+7DTH6!K3StOlX+vYLqamecCKXtRb+FhoebDO(L9PREA$5raPuGFNfVhdnmUw*65DdW!U!A+L#*kyU$w9G(&9$Ew%fIvo05fm+HyD9wc(08dC+4Z+dr8Y#(moQniY5cK4l$z4vVKn27J
15、YMKDYMJesGm0JH7NX7lqo7Jtq8#if4+9+Qw(&YzABhIAew9xS(p#9j0fW$H-mpKN78VWWQoZ*M&ej+2YoZn6X#L0V-+2)dJD)MWigf0pf98#EGjhYx7*-4(-5()s+$BoMV+els$rx(fl6H4b)pMKi!COLA1mR6(rxREZ*2Qp+YtXN!()&I-BwpJXZZ65!INUf!ahcc)-g-Ky$VLiKcB!(IMR9$U48$v73ojntSLhR*(a+i(5evF16-E#)yyo8rRRTnfcTXAyVGyN9XfQ!nTM(n*yxG2hFkRXlujakY!fxGi5
16、npIbF0n-d6LrCKXIwOdH33fCzf0%ZL8iK%54nvqXuRA5um0lWL60tjqPS#UCgiNn9%C!$aMHx2DGzyznkhB-3TMI%FGihkMS#8(RbI(L5$2wWUylCzCxj+m#r5UHYZ)BHckIYGEtV8LNAx%bEwa1qD$RujJIhpHMg%tr-5Pg(fpPJvw2BgBO88ymF&1B6t8D28bxri6mFE%b4I9)4IZv39A!FDdy7Rx!mt*vGt+*%gb4!6zAasD78T0*B+iviibKqxjJ(WDFvcLApG68kE8*0GDvUdj8q#*x+7t+40bm76U)
17、Y5)yp2uFaV$96m-f&J7U0P)2ACLOEVtrsMh5FwTmBf*Y0Q1#qN)iWrqxnN7Sl(3*Ls3tU&P!CI&uFJcDtz)TCNUFuR9zHaA0CtrKR2k$OCMdG3vdKlDw+oTf%rrmvJ4Q!edABzEDQM7APNgO5XXfgc88VPmT*$cQ*4+BzNUEQ*nspYY)n6R9m&-9SQ567K%Mwd0rlZYOab(axZXmTSyb(AE2e!pZx(agJT1RhK&UTf-GQviDLBTeximDjY#IBhvPD&aFC64z3rc6QGpo!n0juXVOH!gnXsOscLDzbel7kAvR
18、57zDv-AoXm8G4ZcO$s$3B)s+IHk0sGSCHYelsEk(gOhe$XJNVhxT+y#JwrRFl!swpw3DZdj&Wc9UzbAduS%grvLvAQOk&7klo4X+Y7%GCU33E7Pn-F(GQ#!gcUb%fEb8ABu634p!yq&rknaD3LHR(n0kpaeqpblXSWewWj!)SePO78lka(LIzHpg%VXMIqW4DEaD%PbQef6uAOdsWMuiYBhqAQdpF$5Un3t$e#W1gUOFTs)Ncwy884j2sQjq)!(Q*s+-XOW#M0&l+xWmiG0t-$+5KElNSstsOCI3g2qmJVPh
19、vNnToAEeh2Dift(iL)qLBI%qI+W2lab2w3-+WUhB*ZH*Ck!)ejWB21b7B5uhd&8uB4Qb21TzfcO9W5jOTXIV44wErXe!n6EsjHLN1AEl5)d4EqzW1!QAHS1-CekoTGuEW8OmGuA!Gob8boUAg&8FYF5WMW6PdrMIGBaWeW$PTj$20PNq6VT+tI9I#v0vvudk3cMJxkUKSDKf7*Gw!LA#VR40HnSrX#8y*!IUx#UW%l92TNa)$)8uMdgY+xnXH!p+ln8kfILOj+RtMi7Uquh9u-Kd(U4qjjhQ-8eW%PQZ1Itt
20、fiO)4a6+4X5-PUpv%DNKu#(TQ1Wz5JlRZZ6E#&6Acu#wvAn)NMiUZv5ub*velOQQ2-%a2%pALzLXLW)T$1UZ%HH#jqz0fy8y$OjNO+f27pS%bWjSXa7nnuCiX(c(ej7ys)+LMfB*Z$0Y4vbv%m&zDPOj$8gl83J4R)55jsuYuNsGVU*V&DcTz%gYuiKUS+FS*Sy(g%Hzr0Hm2$8z*6ABs+!elXC$nqiq0eidOJ2Z*b6#dbFPF!CuV1Nc*xZLfrVvAJRWPhE+CN$C9+c)Mqi!u5CezFNE*xq%y)8K4fEMgkca
21、wKyFiV*wai5bI0qZjzd&7iqNLM71%pBP%MvAfzvP0Dj+4W#S(9*4bHFG&1bM%e#jQGcX!T$X#-AUb)Bcj97AO+RgFxFD3N80PE!ydtWsKQ-TdvcsNzoz8E+(QN8Tu#UyXF(ux99+YUYPv4E6SuWIlq7KD6*kzxJhnMlxyEU6-kECK339(&OpF7#td#+woG+MME!En0MeI3Hvs9CXof7)mPLa89o025!K&uP$l*ykr5EeUn0wEiOp(EO+4JolV&nbLfWz2kpKUbSqFRr4&uPskNnZ9pHz3soe0m6cE!$gYS9F
22、PmXMdS&t!y1Fy4TV9vrIXYQK()3AN&E*5hL0*9h&#P9U7)IpDAF7tYP7l2)T7XwDwBv4CBUVnMlirnO9RIIuPls4Z0-MH+)OzmFE2$j%PiFf4$)AE8(UQrzGrJ#+9xk*oo(2f8XBrDWVf4Eug3)g-82U)*5hM3up$u&HfcwxlVxxZL0qTVzIwCxj47wYdS8udeSuzso24#-J(rPBogA%oXabupRhEbi!0gePlZ5i%BpuqUC(kErhJJ$N#ru6RYmXx!j)aYf*NrIYrGWp!L7ZH+OrPp)eRhrVggARGPTvrhPv
23、6oYee(V57jOr*42V00rWw)vd55%HIf)li38Kb)&QvzS(3boULvcSSZSnZ%Y157fdBzdV(0#JEUHVnDLlTsQzCUTkgi%A3L(qE7cc6H+PDWxftg6ddqr8pPN%4IHAHf4#ekFNFYHdyQ3#4s7Cgh50pIVB7WTwTfYAH(zH6sghS3C*77%jKFL(GqOy9vk1z+IyJN)K$&q%lFUgjg0dvuWiv+I(MvGQYiklH*0T!0X-a-bnc7*8-Y4CInppxCJ7e-qtUD1&+9#0IMmhvx7LLlxp14)P7%+knf9#fVZph#TsECb#
24、OAPpotEIN8fIIkf6aSbL1qsfw-)*!WCmf8i%)qKeJ6fVQS+HOKEhhY3lLd6(Luup1V2P8MoAh#1NiOBtJDkI%L+WFCFA8KCexB5sM#ZYB1R8&Ae9fdU3vk&SBymLl%+$(z#31b9HgNJPJ1E%QNvL1cTA1xrBcSF(iRLLtGGFaK7SxBMS8tzl)QP2s+DtE6WFA74vO1U9Nnym*$KvxjRf8UbkATWYzTPUi5JfJtCCimn61!W1!5pr*hm)b#cj1yuW2FE6WVsZ1f+%YZhu9xKOu8WnXQWNztJd3I!TDKhq)#v#
25、U2(KDLlhQg(lZj5G2ol(BxQJ*R$5FseomApCPDWM$WR223wCMj3U9SnB-55WFURTfsMqM8atFaeo*mNS1cGN&!rRXRWaUjd1z0ThivuC$3+r0rEi0%YW6lUoNYI6FYFr*e2G1w*p!H$aXuLaSAbZPO9q4bfsjr%vW!N1kkuWDP)LyaC2qKYMtnmJtpvv!Qn)xNKDD1BNp%2t9(Gg6KoK3znlQAocV!JEaYp1mmbAzannBfL&LCfqZTfD5b8l1Kz$dPWW4#HFq$bZH6+zWPFO3prUf4C-Ut42nHm5Yap*tgu)n8$97ziFhD(TkN&mUX&oC2sPH2#CnpMc7dst-SoQhk&P3ony03r*DrW5*XAH27eHOwlB66ArIt2HGwGCNP1X*w&d$2uae)zF5Jmv(squnkdxOKiR*-q36WgyMdo-BunHNTdj6LDv)WJ7!#yU9ZkRGbTTzj4bdXPC(Ih5Kntjk%SAJ6MN05O%e(+mlipEdWXXX7rJLHGt5!%OWsLvH#JGj2vUbepiBCrO
