Movérare Sofia, Dahllund Johanna, Andersson Niklas, Islander Ulrika, Carlsten Hans, Gustafsson Jan-Ake, Nilsson Stefan, Ohlsson Claes
Department of Internal Medicine, Division of Endocrinology, Gröna Stråket 8, 413 45 Gothenburg, Sweden.
Mol Pharmacol. 2003 Dec;64(6):1428-33. doi: 10.1124/mol.64.6.1428.
It was recently reported that the synthetic compound estren increases bone mass without affecting reproductive organs or classic transcription. The aim of the present study was to further characterize the in vivo and in vitro effects of estren. We demonstrate that estren is a selective estrogen receptor modulator (SERM) with a strong effect on thymus, a moderate effect on uterus and trabecular bone, but no major effect on fat or cortical bone in 11-month-old ovariectomized mice. The effect of estren on trabecular bone and uterus is mediated via estrogen receptors (ERs) because no effect is seen in ER double-inactivated mice. Furthermore, with the use of ERalpha- and ERbeta-expressing reporter cell lines, we demonstrate that estren displays an agonistic effect on transcriptional activity of an estrogen-responsive element-driven reporter gene with a degree of agonism similar to that of 17beta-estradiol for both ERalpha and ERbeta. Thus, estren has the capacity to exert genomic effects via both ERalpha and ERbeta. We conclude, in contrast to what was previously reported by others, that estren is a SERM with transcriptional activity.
最近有报道称，合成化合物埃斯特林可增加骨量，而不影响生殖器官或经典转录。本研究的目的是进一步表征埃斯特林的体内和体外效应。我们证明，在11个月大的去卵巢小鼠中，埃斯特林是一种选择性雌激素受体调节剂（SERM），对胸腺有强烈作用，对子宫和小梁骨有中等作用，但对脂肪或皮质骨没有主要影响。埃斯特林对小梁骨和子宫的作用是通过雌激素受体（ERs）介导的，因为在ER双失活小鼠中未观察到作用。此外，通过使用表达ERα和ERβ的报告细胞系，我们证明埃斯特林对雌激素反应元件驱动的报告基因的转录活性具有激动作用，其激动程度与17β-雌二醇对ERα和ERβ的激动程度相似。因此，埃斯特林有能力通过ERα和ERβ发挥基因组效应。我们得出结论，与其他人之前的报道相反，埃斯特林是一种具有转录活性的SERM。
