异体垂体移植大鼠E_2诱致催乳素瘤的实验研究

E_2-Induced Prolactin-Secreting Tumor of Heteroplasty Pituitary in Renal Capsule of the Rats

目的 探讨催乳素瘤的发病机理,验证其原发于腺垂体的假说。方法 应用雄性S.D.大鼠进行异体垂体移植,并通过背部埋植17-β-雌二醇(E_2)药泵,观察E_2对大鼠原位垂体,异体移植于肾囊的垂体及血浆催乳素(prolactin,PRL)水平的影响。并利用上述垂体细胞原代培养及原位杂交组化方法,研究经E_2作用120d后的原位及移植垂体细胞中PRL基因表达水平的改变。结果 经E_2作用60d及120d后,大鼠体重分别降至正常大鼠的74%(P<0.01)和50%(P<0.001),原位垂体及移植垂体的重量则较对照组增加达三倍以上(P<0.001),并伴高催乳素血症,血浆催乳素水平为对照组的100～200倍(P<0.001)。原位杂交结果表明,E_2作用120d后,原位及移植垂体细胞中PRL mRNA水平分别升高为正常大鼠垂体细胞的3.1倍和3.5倍(P<0.001),且二者的表达水平无显著差异。结论 提示E_2也可不经下丘脑机制直接作用于腺垂体水平诱发催乳素瘤,即催乳素瘤有可能原发于腺垂体。但本工作尚未进一步排除催乳素瘤的形成涉及下丘脑机制的可能性。

Objective A prolactin-producing tumor induced by 17-β-estradiol (E_2) in isotransplanted pituitaries under renal capsules of SD rats were studied. Methods Male SD rats (30 days old) were transplanted with an isologaus pituitary under renal capsule and treated with subcutaneous implantation of an empty or E_2-laden silastic capsule. Results After treated with E_2 for 60 days and 120 days,both the eutopic and ectopic pituitaries were more than three times heavier than those from control rats, accompanied by hyperprolactinemia,and the body weight of rats decreased significantly. The effects of E_2 on the weight of eutopic pituitary and the concentration of plasma PRL were time-dependent. In situ hybridization was employed to measure the levels of PRL mRNA expression in cells from the eutopic and ectopic pituitaries 120 days after treatment of E_2. The PRL mRNA contents in both the eutopic and ectopic pituitary cells were much greater than those in untreated pituitary cells. But PRL mRNA levels showed no significant difference between the eutopic and ectopic pituitary cells. Conclusions Our previous data has shown that prolactinomas can be induced by chronic treatment of E_2 in eutopic pituitaries of SD rats. In present study it appeared that E_2 exerted similar effect on the ectopic pituitaries which were distant from the hypothalamus. Our results also demonstrated that E_2 could promote the PRL gene expression in both the eutopic and ectopic pituitary cells, and there was no significant difference between them. Our data suggested the possibility of PRL-producing pituitary tumors could originate from anterior pituitary.