垂体催乳素瘤的病因及发病机制的实验研究  

ExperimentalInvestigationontheEtiologyandPathogenesisofPituitaryProlactin Se cretingTumor

作　　者：吴雪梅[1] 

机构地区：[1]中国协和医科大学基础医学院

出　　处：《生理科学进展》2000年第1期43-46,共4页Progress in Physiological Sciences

摘　　要：应用在同一只雄性SD大鼠中,保留原位垂体并在肾囊内植入一异体垂体,同时背部埋植装有17β雌二醇(17βestradiol,E2)的药泵,经E2在体作用60～120天后,其原位垂体和异体移植入肾囊的垂体同时形成垂体催乳素(prolactin,PRL)瘤的动物模型,研究PRL瘤的发病机制。结果表明,E2长期作用可诱发原位垂体和远离下丘脑的移植垂体同时形成PRL瘤,并伴高PRL血症和PRL基因的高表达;体外和体内实验结果均显示,一些相关生长因子或细胞因子可能与PRL瘤的形成有关;分析正常垂体、原位和移植垂体瘤中PRL基因调控序列的结构,表明在原位垂体瘤中PRL基因近端启动子区发生点突变,突变启动子活性增高,而移植垂体瘤PRL基因相应序列无改变。上述结果提示:垂体PRL瘤可能原发于腺垂体水平,但未排除继发于下丘脑异常的另一可能性;雌激素诱发原位和移植垂体形成PRL瘤的发病机制可能不尽相同;体内神经内分泌免疫网络在原位垂体PRL瘤的发生过程可能起一定作用,但其确切证据尚待深入探讨。MaleSDratstransplantedwithanextrapituitaryintherenalcapsuleand treatedchronicallywith 1 7 β estradiol(E2 )wereusedinthestudiesonthepathogenesis andtheunderlyingmechanismsofpituitaryprolactin secretingtumor ( prolactinoma) . TheresultsindicatedthatafterlongtreatmentwithE2 ,prolactin secretingtumorwas generatedinbotheutopicandectopicpituitary ,accompaniedbyhyperprolactinemiaandoverexpressionofPRLgene .Noapparentdifferencewasobservedinhistologyandul trastructurebetweenthem .Furtherinvestigationsshowedthatsomegrowthfactors mightbeinvolvedinthetumorigenesisofprolactinomainvivoandinvitro .Apoint mutationwasfoundintheproximalpromoterofPRLgeneonlyineutopicprolactinoma bypolymerasechainreaction single strandconformationpolymorphism (PCR SSCP) ,suggestingthatthebasechangeinthepromotermayberelatedtotheoverexpressionof PRLgene.Thishypothesishasbeenconfirmedbytheincreasedactivityofluciferasere porterfusedtothemutantpromoterinvitro .Thecoincidenceofoverexpressionof PRL ,TGFαandTGFβ1 gene ,andthepointmutationdetectedineutopicpituitarypro lactinomasuggestedthatneuro endocrine immuneinteractionsinvivomightbeassociat edwithpituitaryprolactinomaformation .Themechanismsmediatingtumorigenesisof eutopicandectopicprolactinoma ,respectively ,maybedifferent.

关 键 词：17-Β-雌二醇 垂体催乳素瘤 病因 发病机制 腺垂 

分 类 号：R736.402[医药卫生—肿瘤]