Wang K S, Hodgetts R B, Addison W R
Department of Biological Sciences, University of Alberta, Edmonton, Canada.
J Mol Endocrinol. 1998 Feb;20(1):141-50. doi: 10.1677/jme.0.0200141.
Expression of the rat alpha 2u-globulin gene family is regulated in the adult male liver by a number of hormones, including growth hormone, thyroid hormone and several steroids. Upon injection into ovariectomized females, estrogens first induce alpha 2u-globulin expression and then suppress this gene after several days of hormone administration. To study this phenomenon, we developed a mouse L-cell line that expressed the human estrogen receptor. High levels of rat alpha 2u-globulin transcript were induced in stable transfectants of this line carrying a cloned alpha 2u-globulin gene, following exposure to 17 beta-estradiol. Since this induction was inhibited by cycloheximide, the response to estrogen, as to other steroids, appears to be secondary. Using genes with variously deleted 5'-upstream regions, sequences responsible for this induction were located between -730 bp and -223 bp relative to the start of transcription. Examination of the DNA in this region revealed that an estrogen receptor element was located at -590 bp in an area that is highly conserved in most known alpha 2u-globulin genes. Administration of both dexamethasone and estrogen produced a synergistic effect in this system. The induction of alpha 2u-globulin RNA by estrogen in L-cells may re-capitulate the initial response to estrogen in vivo, and therefore represents a good model system to seek the identity of the other factors required to effect full induction.
大鼠α2u -球蛋白基因家族的表达在成年雄性肝脏中受到多种激素的调控，包括生长激素、甲状腺激素和几种甾体激素。将雌激素注射到去卵巢雌性大鼠体内后，雌激素首先诱导α2u -球蛋白的表达，然后在给药几天后抑制该基因的表达。为了研究这一现象，我们构建了一种表达人雌激素受体的小鼠L细胞系。在携带克隆的α2u -球蛋白基因的该细胞系的稳定转染子中，暴露于17β -雌二醇后可诱导出高水平的大鼠α2u -球蛋白转录本。由于这种诱导被放线菌酮抑制，因此对雌激素的反应，与对其他甾体激素的反应一样，似乎是继发性的。利用具有不同5' -上游区域缺失的基因，负责这种诱导的序列定位于相对于转录起始点的 - 730 bp至 - 223 bp之间。对该区域DNA的检查发现，一个雌激素受体元件位于 - 590 bp处，该区域在大多数已知的α2u -球蛋白基因中高度保守。地塞米松和雌激素同时给药在该系统中产生协同效应。雌激素在L细胞中诱导α2u -球蛋白RNA可能重现了体内对雌激素的初始反应，因此代表了一个很好的模型系统，用于寻找实现完全诱导所需的其他因子的身份。
