Progestin represses human connexin43 gene expression similarly in primary cultures of myometrial and uterine leiomyoma cells.
Progestin represses human connexin43 gene expression similarly in primary cultures of myometrial and uterine leiomyoma cells.
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孕激素在子宫肌瘤细胞和子宫肌瘤细胞的原代培养物中类似地抑制人连接蛋白 43 基因表达。
DOI：
10.1095/biolreprod54.3.607
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发表时间：
1996
影响因子：
3.6
通讯作者：
Andersen,J
中科院分区：
文献类型：
--
作者：
Zhao,K;Kuperman,L;Geimonen,E;Andersen,J
在人子宫肌瘤细胞原代培养物中分析了黄体酮抑制人连接蛋白43 （cx43）基因表达的机制，并与子宫平滑肌瘤细胞原代培养物进行了比较。在24小时内，孕激素处理的原代细胞中的Cx43蛋白水平降低到未处理细胞的50%左右，并且这种水平维持了120小时。在孕激素浓度为50-100 nM时，Cx43蛋白水平的降低达到平台期。在自体子宫肌瘤和平滑肌瘤原代培养中，比较孕激素介导的Cx43蛋白的减少没有发现显著差异。在子宫肌瘤和平滑肌瘤细胞中，使用黄体酮治疗数小时后，cx43mrna水平也下降了约50%，并且这些新的水平维持了48小时。核运行转录分析显示，100 nM黄体酮在子宫肌瘤和平滑肌瘤原代培养中部分抑制x43基因的转录。在黄体酮处理的细胞中，incx43转录的减少量与细胞质cx43mrna水平的相应降低相一致。孕激素受体（PR）介导的转录在两种类型的原代细胞中也被确定为相似，这一点通过瞬时表达实验得到了证实。因此，黄体酮主要通过抑制子宫肌瘤细胞中该基因的转录来下调humancx43基因的表达，在平滑肌瘤细胞中也有类似的作用。
The mechanism by which progestin represses the expression of the human connexin43 (cx43) gene was analyzed in primary cultures of human myometrial cells, and for comparison, in primary cultures of uterine leiomyoma cells. Within 24 h, the levels of connexin43 (Cx43) protein in primary cells treated with progestin were reduced to about 50% of that in untreated cells, and these levels were maintained for up to 120 h. A plateau in the reduction of Cx43 protein levels was reached at progestin concentrations of 50–100 nM. No significant difference was found in a comparison of progestin-mediated reduction of Cx43 protein in autologous myometrial and leiomyoma primary cultures. Levels ofcx43mRNA levels also decreased to about 50% in myometrial and leiomyoma cells within hours after treatment with progestin, and these new levels were maintained for up to 48 h. Nuclear run-on transcription analysis showed that 100 nM progestin partially repressed transcription of thecx43gene in both myometrial and leiomyoma primary cultures. The amount of decrease incx43transcription in cells treated with progestin was paralleled by a corresponding decrease in cytoplasmiccx43mRNA levels. Progesterone receptor (PR)-mediated transcription was also determined to be similar in the two types of primary cells as evidenced by transient expression assays. Thus progestin down-regulates the expression of the humancx43gene primarily by repressing transcription of the gene in myometrial cells, and it acts similarly in leiomyoma cells.