Transcriptional regulation of estrogen-responsive genes by non-steroidal estrogens: doisynolic and allenolic acids.
Transcriptional regulation of estrogen-responsive genes by non-steroidal estrogens: doisynolic and allenolic acids.
复制标题
非甾体雌激素对雌激素反应基因的转录调节：异辛醇酸和联烯酸。
DOI：
10.1016/s0960-0760(97)00063-0
复制
发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Adler,S
中科院分区：
文献类型：
--
作者：
Meyers,CY;Lutfi,HG;Adler,S
Estrogen receptor (ER), a member of the nuclear receptor superfamily, exerts prominent physiological roles in both humans and other species by acting directly as a transcription factor, altering nuclear gene expression. One peculiarity of estrogenic regulation is that it is affected by a wide variety of non-steroidal compounds in addition to the natural hormone, estradiol. Doisynolic and allenolic acid compounds are non-steroidal compounds that act as potent estrogens in animal studies, yet bind to ER extremely poorly in competitive binding assays, raising the possibility of alternative molecular mechanisms for the observed estrogenic effects. In this work we demonstrate that (±)-Z-bisdehydrodoisynolic acid, (±)-Z-bisdehydrodoisynolic acid 3-methyl ether, and (−) allenolic acid can interact directly with ER. These compounds all serve as ligands for ER in mechanism-specific tissue culture-based reporter gene assays for both positive and negative gene regulation. We have also used a novel assay based on electromobility shift by ER for directly determining relative binding affinities for ER. In addition, we show cell-type-specific activity differences for (±)-Z-bisdehydrodoisynolic acid 3-methyl ether, supporting clinical observations indicating a higher potency of this compound in female animals than in humans.
