動情素及環境動情素影響成骨細胞生長之機轉研究

Abstract

動情素(estrogen)在生理病理上 有其特殊意義，對於骨骼也具有保 護作用，但其需透過何種機制來進 行則尚未完全清楚。環境動情素 (environmental estrogens) 包括有去污 劑、殺蟲劑、其他工業化學物如多 氯聯苯(hydroxy-PCBs)、2,3,4-TCB、 4-OH-alkyl-phenols、多環芳香烴類化 合物等，以及緣自植物的phytosterol esters，已知其中某些物質會與細胞 核類固醇受體交互作用而影響到性 分化現象。雖然目前對於環境動情 素在內分泌及生殖系統的影響有較 多的研究，但這些賀爾蒙樣物質對 於骨代謝系統的影響也是不容忽 視，而有關此方面的研究並不多。 在本研究計劃中，我們發現動情素 樣物質會促進初級培養成骨細胞 (primary culture of rat osteoblast-like cells) 及人類成骨細胞株(MG-63 cells)增 生，此作用會被ICI182,780 (動情素 拮抗劑)對抗。動情素樣物質亦會促 進成骨細胞ERK1/2蛋白磷酸化及誘 導二型環氧酵素(cyclooxygenase-2)表 現。MAP kinase 抑制劑PD98059 會對 抗動情素樣物質引起的二型環氧酵 素及細胞增生表現。這些結果顯示 MAP kinase 系中之ERK1/2 參與動情 素樣物質引起的二型環氧酵素及細 胞增生表現過程。

It has been found that estrogen had protective effects on bone, but the mechanisms of action have not been fully established. Environmental estrogens include the detergents, pesticide, chlorinated insecticides, polycyclic aromatic hydrocarbons and phytosterol esters, and some of these compounds have recently been reported to modulate sexual differentiation by interacting with nuclear steroid receptors. There is an ongoing scientific debate concerning the potential threat of environmental estrogenic pollutants to animal and human health. So far, the focus has been on endocrinological system and reproductive organs, but environmental estrogens have far more widespread actions like as bone system. Nevertheless, the literatures about the action of these substances on the bone system are rare. In our study, we found that environmental estrogens were capable of increasing the proliferation in primary culture of rat osteoblast-like cells and human osteoblast-like cell line (MG-63), which could be blocked by estrogen antagonist (ICI182,780). Moreover, these environment estrogens could also trigger the phosphorylation of ERK1/2 and could induce the protein expression of cyclooxygenase-2 (COX-2) in osteoblasts. MAP kinase inhibitor PD98059 was capable of inhibiting the expression of COX-2 and cell proliferation induced by these environmental estrogens. These results indicate that the MAP kinase pathway may be involved in environment estrogens-induced COX-2 expression and cell proliferation in osteoblasts