Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 64239, Israel.
J Steroid Biochem Mol Biol. 2011 Jul;125(3-5):226-30. doi: 10.1016/j.jsbmb.2011.03.006. Epub 2011 Mar 21.
We have previously reported that human cultured bone cells (hObs) respond to estradiol-17β (E2) by stimulating DNA synthesis, creatine kinase BB specific activity (CK) and other parameters sex-specifically. We now investigate the sex specificity of the response of these hObs to estrogen receptor (ER) α and ERβ specific agonists. Real time PCR revealed that all cells express mRNA for both ERs. ERα mRNA but not ERβ mRNA was stimulated by all estrogenic compounds in both pre- and post-menopausal hObs with no effect in male hObs. Cells treated with E2, 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN; ERβ specific agonist) and 4,4',4″-[4-propyl-(1H)-pyrazol-1,3,5-triyl] tris-phenol (PPT; ERα specific agonist) showed increased DNA synthesis and CK in all female but not male hObs. Raloxifene (Ral), a specific ERα antagonist, inhibited the stimulation of DNA synthesis and CK by E2 or PPT, but not by DPN. DPN and PPT like E2 modulated the expression of both 12 and 15 lipooxygenase (LO) mRNA in both female but not male hObs. 12 and 15 HETE production was modulated only by DPN and PPT in these cells. The LO inhibitor baicaleine inhibited only E2 and PPT but not DPN effects in both female hObs. In conclusion, we provide herein evidence for the separation of age- and sex-dependent mediation via both ERα and ERβ pathways in the effects of estrogens on hObs, with a yet unknown mechanism.
我们之前曾报道过，人类培养的骨细胞（hObs）通过刺激 DNA 合成、肌酸激酶 BB 比活性（CK）和其他参数来对雌二醇-17β（E2）做出反应，这些参数具有性别特异性。我们现在研究这些 hObs 对雌激素受体（ER）α和 ERβ 特异性激动剂反应的性别特异性。实时 PCR 显示所有细胞均表达两种 ER 的 mRNA。所有雌激素化合物均能刺激绝经前和绝经后 hObs 中的 ERα mRNA，但不能刺激男性 hObs 中的 ERα mRNA。用 E2、2,3-双（4-羟苯基）丙腈（DPN；ERβ 特异性激动剂）和 4,4',4″-[4-丙基-（1H）-吡唑-1,3,5-三基]三苯酚（PPT；ERα 特异性激动剂）处理的细胞显示 DNA 合成和 CK 在所有女性 hObs 中增加，但在男性 hObs 中则没有。雷洛昔芬（Ral），一种特异性 ERα 拮抗剂，抑制了 E2 或 PPT 对 DNA 合成和 CK 的刺激，但对 DPN 没有抑制作用。DPN 和 PPT 像 E2 一样调节了两种 12 和 15 脂氧合酶（LO）mRNA 在所有女性 hObs 中的表达，但在男性 hObs 中则没有。这些细胞中只有 DPN 和 PPT 调节 12 和 15 HETE 的产生。LO 抑制剂黄芩素仅抑制 E2 和 PPT，但不抑制 DPN 在两种女性 hObs 中的作用。总之，我们在此提供了证据，证明在雌激素对 hObs 的作用中，年龄和性别依赖性的调节是通过 ERα 和 ERβ 途径分开的，其机制尚不清楚。
