Agonistic activity of tamoxifen, a selective estrogen-receptor modulator (SERM), on arthritic ovariectomized mice

Arthritis is positively associated with the decline of sex hormones, especially estrogen. Tamoxifen (TMX) is a selective estrogen receptor modulator, possessing agonist or antagonistic activity in different tissues. Thus, the objective of this study was to investigate the effect of TMX on the zymosan-induced arthritis model. Female Swiss normal and ovariectomized (OVX) mice were divided into groups and treated for five days with TMX (0.3, 0.9 or 2.7 mg/kg) or 17-β-estradiol (E2, 50 µg/kg). On the fifth day, arthritis was induced and 4 h later, leukocyte migration into joint cavities was evaluated. The neutrophil migration in OVX animals, but not in normal mice, treated with TMX (all tested doses) was significantly decreased compared with mice that received the vehicle (P≤0.05). Similarly, this effect was also demonstrated in the E2-treated group. Therefore, the present study demonstrates that TMX presented agonist effects in inhibiting neutrophil migration and preventing arthritis progression in OVX mice.

关节炎(Arthritis)与性激素水平的下降呈正相关，尤以雌激素(estrogen)最为显著。他莫昔芬(Tamoxifen, TMX)作为选择性雌激素受体调节剂，可在不同组织中表现出激动或拮抗活性。因此，本研究旨在探讨他莫昔芬对酵母聚糖诱导的关节炎模型的影响。将雌性瑞士正常小鼠与卵巢切除(ovariectomized, OVX)小鼠分组，分别以他莫昔芬（0.3、0.9或2.7 mg/kg）或17β-雌二醇(17-β-estradiol, E2, 50 µg/kg)连续处理5天。于第5天诱导关节炎造模，造模4小时后评估白细胞向关节腔的迁移情况。与给予溶媒(vehicle)对照的小鼠相比，经他莫昔芬（所有受试剂量）处理的卵巢切除小鼠的中性粒细胞迁移水平显著降低（P≤0.05），而正常小鼠未观察到此效应。类似地，17β-雌二醇处理组也表现出该效应。综上，本研究证实，他莫昔芬在卵巢切除小鼠中可发挥激动剂样作用，抑制中性粒细胞迁移并延缓关节炎进展。