Dipartimento Farmaco-Biologico, Università della Calabria, Rende (CS), Italy.
Mol Cell Endocrinol. 2010 May 14;320(1-2):162-70. doi: 10.1016/j.mce.2010.02.006. Epub 2010 Feb 6.
Estrogens are structurally related steroids that regulate important physiological processes. 17beta-estradiol (E2) is reversibly oxidized to estrone (E1) and both E2 and E1 can be irreversibly converted to estriol (E3), which also originates directly from androstenedione. The action of E2 has been traditionally explained by the binding to the estrogen receptor (ER) alpha and ER beta, however the G protein-coupled receptor (GPR) 30 has been recently involved in the rapid signaling triggered by estrogens. Although the role of E2 in the development of breast cancer has been largely documented, the contribution of E3 still remains to be completely evaluated. Here, we demonstrate for the first time that E3 acts as a GPR30 antagonist since it was able to inhibit the GPR30-mediated responses such as the rapid ERK activation, the up-regulation of target genes like c-fos and connective tissue growth factor, the proliferative effects observed in ER-negative SkBr3 cells.
雌激素是一类具有结构相关性的甾体激素，能调节重要的生理过程。17β-雌二醇（E2）可被可逆氧化为雌酮（E1），E2 和 E1 也可被不可逆地转化为雌三醇（E3），E3 也可直接来源于雄烯二酮。E2 的作用传统上可通过与雌激素受体（ER）α和 ERβ结合来解释，然而，G 蛋白偶联受体（GPR）30 最近也被牵涉到雌激素引发的快速信号转导中。虽然 E2 在乳腺癌发展中的作用已被大量记录，但 E3 的作用仍有待完全评估。在这里，我们首次证明 E3 作为 GPR30 拮抗剂发挥作用，因为它能够抑制 GPR30 介导的反应，如快速 ERK 激活、靶基因如 c-fos 和结缔组织生长因子的上调以及在 ER 阴性 SkBr3 细胞中观察到的增殖作用。
