Zhu Yan, Qiu Xiao-Yan, Wang Lei, Wu Jian-Hui, Liu Gui-Ming, He Gui-Lin, Jiang Xiu-Rong, Sun Zu-Yue, Cao Lin
Shanghai Medical College, Fudan University, Shanghai 200032, China.
Acta Pharmacol Sin. 2007 May;28(5):685-94. doi: 10.1111/j.1745-7254.2007.00537.x.
To investigate the effect of gestrinone on uterine leiomyomas and the expression of c-Src, estradiol receptors (ER), and progesterone receptors (PR) in a guinea pig model.
After being oophorectomized, the guinea pigs were allocated into random groups. The model group was treated with estradiol benzoate (E2) for 16 weeks. In the gestrinone-treated groups, the animals were treated with E2 for 6 weeks in advance, and then in combination with gestrinone for 10 weeks. Histological examination was performed to evaluate whether there were leiomyoma features in the animals. The protein levels of c-Src, phospho-( 416)Src, ER, and PR were assayed by Western blotting and an immunohistochemical method.
Morphological changes were observed in the myometrium of the guinea pig model, including an increase of uterine weights, proliferation of uterine smooth muscles, and the formation of nodules. High protein levels of c-Src, phospho- 416Src, ER, and PR were observed in the myometrium of the guinea pig model. In the gestrinone-treated group, there were no nodules observed. The histological features of the myometrium were similar to that of the control group. Low protein levels of c-Src, phospho-(416 )Src, ER, and PR were observed in the gestrinonetreated group.
The upregulation of c-Src and phospho-(416 )Src indicated that the activity of c-Src is augmented in the uterine leiomyoma model. c-Src was associated with the formation of uterine leiomyomas in the model, and gestrinone markedly suppressed the growth of uterine leiomyomas in the model. Gestrinone inhibited not only the protein expression of ER and PR, but also c-Src and the autophosphorylation of c-Src in the guinea pig leiomyoma model.
在豚鼠模型中研究孕三烯酮对子宫平滑肌瘤以及c-Src、雌二醇受体（孕酮受体表达的影响。
豚鼠卵巢切除术后，随机分组。模型组用苯甲酸雌二醇（E2）治疗16周。在孕三烯酮治疗组中，动物先提前用E2治疗6周，然后联合孕三烯酮治疗10周。进行组织学检查以评估动物是否有平滑肌瘤特征。通过蛋白质印迹法和免疫组织化学方法检测c-Src、磷酸化（416）Src、ER和PR的蛋白水平。
在豚鼠模型的子宫肌层中观察到形态学变化，包括子宫重量增加、子宫平滑肌增殖和结节形成。在豚鼠模型的子宫肌层中观察到c-Src、磷酸化416Src、ER和PR的高蛋白水平。在孕三烯酮治疗组中，未观察到结节。子宫肌层的组织学特征与对照组相似。在孕三烯酮治疗组中观察到c-Src、磷酸化（416）Src、ER和PR的低蛋白水平。
c-Src和磷酸化（416）Src的上调表明子宫平滑肌瘤模型中c-Src的活性增强。在该模型中，c-Src与子宫平滑肌瘤的形成有关，孕三烯酮显著抑制该模型中子宫平滑肌瘤的生长。在豚鼠平滑肌瘤模型中，孕三烯酮不仅抑制ER和PR的蛋白表达，还抑制c-Src及其自身磷酸化。
