Roles of estrogen and progesterone in vascular endothelial growth factor (VEGF) production and endometrial angiogenesis: a study with in vitro and in vivo approaches

• Main Authors: Li-Hsun Chen, 陳立珣
• Other Authors: Yen-Jen Sung
• Format: Others
• Language: en_US
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/24341837249595359170

碩士 === 國立陽明大學 === 解剖暨細胞生物學研究所 === 95 === During normal menstrual cycle, estrogen (EB2B) and progesterone (PB4B) regulate endometrial angiogenesis that is important for successful embryo implantation. Although EB2B have been shown to stimulate endometrial production of vascular endothelial growth factor (VEGF) and subsequent angiogenesis, the role of progesterone in facilitating estrogen-induced angiogenesis remains unclear. Moreover, the hemodynamic effects of EB2B and PB4B on the human endometrium have not been confirmed. This study aimed to investigate the effects of EB2B and PB4B on endometrial proliferation and VEGF production in vitro as well as the hemodynamic changes induced by EB2B and PB4B treatment in vivo. To examine the effects of EB2B and PB4B on the endometrial epithelial cells (EEC), we utilized Ishikawa and Ishikawa02 cells that are positive and negative for estrogen receptor (ER) expression, respectively. Treatment with EB2B and PB4B significantly increased cell proliferation in Ishikawa but not Ishikawa02 cells. Interestingly, EB2B and PB4B could synergistically enhance VEGF production in Ishikawa cells. The EB2B/PB4B-induced VEGF secretion could be inhibited by the ER antagonist ICI182780, but not by the progesterone receptor antagonist RU486. Furthermore, the promoting effect of EB2B and PB4B on VEGF expression was not found in Ishikawa02 cells. Then we examined the effects of VEGF on trophoblast expansion and migration. Using BeWo trophoblast line, trophoblast expansion and migration were shown to be unaffected by VEGF treatment. Finally, the hemodynamic effects of cyclic estradiol and progestin treatment in early menopausal women were examined by three-dimensional power Doppler angiography (3D-PDA). The recruited patients received 11 days of estradiol (phase E) followed by 10 days of estradiol and progestin (phase E/P). Two different progestins were used, i.e., the androgenic norethisterone acetate and the anti-androgenic cyproterone acetate. There was a trend toward an increase in the endometrial volume in phase E and phase E/P, as compared with the phase 0 (before treatment). In patients receiving cyclic estradiol and norethisterone acetate, subendometrial vascular indices displayed increasing tendencies in phase E/P as compared with phase 0, which was not the case in patients taking cyclic estradiol and cyproterone acetate. Our results established that estrogen and progesterone synergistically enhanced VEGF production in an ER-dependent manner and further demonstrated the angiogenesis effect of estrogen and progesterone in vivo, findings that may be important for understanding endometrial preparation for implantation.