Effects of gestrinone on uterine leiomyoma and expression of c-Src in a guinea pig model

• DOI: 10.1111/j.1745-7254.2007.00537.x
• Publication Date: 2007-05-08T11:35:36Z
• Authors: Yan ZHU; Xiao-yan QIU; Lei WANG; Jian-hui WU; Gui-ming LIU; Gui-lin HE; Xiu-rong JIANG; Zu-yue SUN; Lin CAO
• Keywords: Gestrinone; Models, Molecular; 0303 health sciences; Leiomyoma; Ovariectomy; Guinea Pigs; Uterus; Gene Expression; Protein-Tyrosine Kinases; 3. Good health; CSK Tyrosine-Protein Kinase; Random Allocation; 03 medical and health sciences; src-Family Kinases; Uterine Neoplasms; Animals; Female; Progestins

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.