Seidlová-Wuttke D, Becker T, Christoffel V, Jarry H, Wuttke W
Department of Clinical and Experimental Endocrinology, University of Goettingen, Robert-Koch-Strasse 40, 37075 Goettingen, Germany.
J Steroid Biochem Mol Biol. 2003 Aug;86(2):179-88. doi: 10.1016/s0960-0760(03)00270-x.
Silymarin is a widely used standardized mixture of flavonolignans and its major component Silybinin binds to cytosolic estrogen receptors. Here, we demonstrate that this binding is exclusive to the estrogen receptor beta (ERbeta). Treatment of ovariectomized (ovx) rats with silymarin or estradiol (E2) may allow differentiation of biological effects mediated by the ERalpha or ERbeta. E2 inhibited serum LH, cholesterol, LDL and HDL concentrations in the blood and increased gene expression of IGF1, HbEGF and C3 in the uterus, while silymarin was totally ineffective or antagonistic in altering these parameters. Both, E2 and silymarin inhibited expression of uterine ERbeta gene. Hence, in the pituitary, liver (where the lipoproteins are synthesized) and uterus E2 acts primarily via the ERalpha. Exclusive estrogenic effects of silymarin were observed in the metaphysis of the femur (MF), on osteoblast parameters (gene expression of IGF1, TGFbeta1, osteoprotegerin, collagen-1alpha1, osteocalcin (OC)) and on the osteoclast activity marker tartrate resistant acid phosphatase (TRAP) gene expression of adult ovx rats. Our RT-PCR method detects ERbeta gene expression in all organs including developing bones but not in the MF of adult ovx rats. We conclude therefore, that the effects of silymarin in this part of the bone cannot be exerted via the ERalpha because it does not bind to this receptor subtype. Despite the failure to detect ERbeta mRNA in the MF of our animals the possibility exists that ERbeta protein is present and may mediate the effects of silymarin. Another possibility may be that the effect of silymarin and therefore possibly also of E2 in the MF may be mediated via other possibly not yet identified receptors or via an ERbeta splice variant which is not detected by our PCR-method.
水飞蓟素是一种广泛使用的黄酮木脂素标准化混合物，其主要成分水飞蓟宾能与胞质雌激素受体结合。在此，我们证明这种结合仅针对雌激素受体β（ERβ）。用 水飞蓟素或雌二醇（E2）处理去卵巢（ovx）大鼠，可能有助于区分由 ERα 或 ERβ 介导的生物学效应。E2 可抑制血液中血清促黄体生成素（LH）、胆固醇、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）的浓度，并增加子宫中胰岛素样生长因子 1（IGF1）、肝素结合表皮生长因子（HbEGF）和补体 3（C3）的基因表达，而水飞蓟素在改变这些参数方面完全无效或具有拮抗作用。E2 和水飞蓟素均抑制子宫 ERβ 基因的表达。因此，在垂体、肝脏（脂蛋白在此合成）和子宫中，E2 主要通过 ERα 发挥作用。在成年去卵巢大鼠的股骨 metaphysis（MF）中观察到了水飞蓟素独特的雌激素效应，对成骨细胞参数（IGF1、转化生长因子β1（TGFβ1）、骨保护素、胶原蛋白 - 1α1、骨钙素（OC）的基因表达）以及破骨细胞活性标志物抗酒石酸酸性磷酸酶（TRAP）基因表达有影响。我们的逆转录 - 聚合酶链反应（RT - PCR）方法可检测包括发育中的骨骼在内的所有器官中的 ERβ 基因表达，但在成年去卵巢大鼠的 MF 中未检测到。因此，我们得出结论，水飞蓟素在骨骼这一部分的作用不可能通过 ERα 发挥，因为它不与该受体亚型结合。尽管在我们动物的 MF 中未能检测到 ERβ mRNA，但存在 ERβ 蛋白存在并可能介导水飞蓟素效应的可能性。另一种可能性可能是，水飞蓟素以及因此可能还有 E2 在 MF 中的作用可能通过其他可能尚未确定的受体介导，或者通过我们的 PCR 方法未检测到的 ERβ 剪接变体介导。
