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 To investigate the pathogenesis of prolactinoma and verify its hypothesis of primary pituitary gland. Methods Male SD rats were used for allograft transplantation and 17-β-estradiol (E_2) pump was implanted on the back to observe the effects of E_2 on orthotopic pituitary gland and allograft in the pituitary gland and plasma prolactin. The effect of prolactin, PRL) levels. The primary culture of pituitary cells and the in situ hybridization histochemical method were used to study the changes of PRL gene expression in situ and in pituitary cells after 120 days of E 2 exposure. Results After 60 days and 120 days of E_2 administration, the body weight of rats decreased to 74% (P<0.01) and 50% (P<0.001) of normal rats, respectively. The weight of orthotopic pituitary and pituitary glands increased by three times compared with the control group. More than doubled (P<0.001), with hyperprolactinemia, plasma prolactin levels were 100-200-fold higher than in the control group (P<0.001). The results of in situ hybridization showed that after 120 days of E 2 , the mRNA level of PRL in the orthotopically transplanted pituitary cells was increased 3.1 times and 3.5 times (P<0.001), respectively, in normal pituitary cells, and there was no significant difference in the expression level of PRL mRNA. difference. Conclusion It is suggested that E2 can also induce prolactinoma directly at the level of adenohypophysis without the hypothalamic mechanism, that is, prolactinoma may be primary in the pituitary gland. However, this work has not further ruled out the possibility that the formation of prolactinoma involves the hypothalamus mechanism.