Maruyama K, Endoh H, Sasaki-Iwaoka H, Kanou H, Shimaya E, Hashimoto S, Kato S, Kawashima H
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Biochem Biophys Res Commun. 1998 May 8;246(1):142-7. doi: 10.1006/bbrc.1998.8590.
A novel isoform of rat estrogen receptor (ER) beta, ER beta 2, which is a putative alternative splicing product of the reported ER beta (ER beta 1) has been identified. Rat ER beta 2 cDNA contains an additional, in-frame 54 base pair insertion in the ligand binding domain of ER beta 1, which generates an 18 amino acid residue insertion. Northern blot and RT-PCR analyses revealed that ER beta 2 coexists with ER alpha and ER beta 1 in all tissues examined including brain, lung, liver, kidney, fat, bone, uterus, prostate, and ovary. The insertion caused loss of ligand binding activity of ER beta 2, whereas the ability to bind the palindromic estrogen response element (ERE) was retained. In an ERE-containing luciferase reporter gene assay using COS-1 cells, ER beta 2 failed to activate estrogen-dependent transcription. Furthermore, ER beta 2 dose dependently suppressed the ER alpha- and ER beta 1-mediated transcriptional activation. These results suggest that rat ER beta 2 functions as a negative regulator of estrogen action.
已鉴定出大鼠雌激素受体（ER）β的一种新型异构体ERβ2，它被认为是已报道的ERβ（ERβ1）的一种选择性剪接产物。大鼠ERβ2 cDNA在ERβ1的配体结合域中含有一个额外的、读码框内的54个碱基对的插入片段，这导致了18个氨基酸残基的插入。Northern印迹和逆转录-聚合酶链反应（RT-PCR）分析表明，ERβ2与ERα和ERβ1在包括脑、肺、肝、肾、脂肪、骨、子宫、前列腺和卵巢在内的所有检测组织中共存。该插入导致ERβ2的配体结合活性丧失，而与回文雌激素反应元件（ERE）结合的能力得以保留。在使用COS-1细胞的含ERE的荧光素酶报告基因测定中，ERβ2未能激活雌激素依赖性转录。此外，ERβ2剂量依赖性地抑制ERα和ERβ1介导的转录激活。这些结果表明，大鼠ERβ2作为雌激素作用的负调节因子发挥作用。
