RETINOIC ACID INHIBITS ESTROGEN-INDUCED UTERINE STROMAL AND MYOMETRIAL CELL PROLIFERATIONS
RETINOIC ACID INHIBITS ESTROGEN-INDUCED UTERINE STROMAL AND MYOMETRIAL CELL PROLIFERATIONS
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DOI：
10.1210/en.136.7.2975
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发表时间：
1995-07-01
期刊：
影响因子：
4.8
通讯作者：
STANCEL, GM
中科院分区：
文献类型：
--
作者：
BOETTGERTONG, HL;STANCEL, GM
维甲酸是维生素A的一种强有力的天然衍生物，影响许多细胞类型的增殖。然而，在正常生理系统中，维甲酸在雌激素诱导的细胞增殖中的作用知之甚少。在这项研究中，我们试图确定体内给予维甲酸是否影响正常雌激素靶组织-未成熟大鼠子宫的增殖。结果表明，在给予17β-雌二醇(E(2))前给动物30 mg/kg全反式维甲酸3天，可使子宫间质和子宫肌层细胞的DNA合成和细胞分裂减少约50%。腔上皮细胞的增殖没有受到抑制，这表明全反式维甲酸的抗增殖作用是针对特定细胞类型的。这种抑制是维甲酸专一性的，在停止全反式维甲酸治疗一周后完全可逆。全反式维甲酸的抑制作用不是由于通过配基结合评估E(2)受体水平的变化。E(2)c-jun基因的诱导在维甲酸处理的动物中不受影响，该基因主要在子宫肌层细胞中表达。这是首次证明维甲酸在生理环境下抑制雌激素诱导的子宫间质和子宫肌层细胞的增殖。
Retinoic acid, a potent natural derivative of vitamin A, influences proliferation in many cell types. However, little is known about the role of retinoic acid in estrogen-induced proliferation in normal physiological systems. In this study we sought to determine if in vivo administration of retinoic acid influences the proliferation of a normal estrogen target tissue, the immature rat uterus. The results indicate that treatment of animals with 30 mg/kg all-trans-retinoic acid for 3 days before 17 beta-estradiol (E(2)) administration diminishes DNA synthesis and cell division by approximately 50% in uterine stromal and myometrial cells. Luminal epithelial cell proliferation is not inhibited, indicating that the antiproliferative effects of all-trans-retinoic acid treatment are cell type-specific. The inhibition is retinoid-specific and fully reversible 1 week after discontinuing all-trans-retinoic acid treatment. The inhibitory effect of all-trans-retinoic acid is not due to a change in E(2) receptor levels assessed by Ligand binding. E(2) induction of c-jun, a gene expressed primarily in myometrial cells, is unaffected in retinoid-treated animals. This is the first demonstration that retinoic acid inhibits estrogen-induced proliferation of uterine stromal and myometrial cells in a physiological setting.