Effects of dienogest, a synthetic steroid, on experimental endometriosis in rats
Effects of dienogest, a synthetic steroid, on experimental endometriosis in rats
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DOI：
10.1530/eje.0.1380216
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发表时间：
1998-02-01
影响因子：
5.8
通讯作者：
Nozawa, S
中科院分区：
文献类型：
--
作者：
Katsuki, Y;Takano, Y;Nozawa, S
目的：地诺孕素是一种具有促孕活性的合成类固醇，被用作口服避孕药的成分，目前正在临床上评估其治疗子宫内膜异位症的效果。目的：观察地诺孕素（Dienogest）对大鼠子宫内膜异位症的治疗作用，并探讨其作用机制。方法：采用大鼠自体子宫内膜移植模型，观察地诺孕素对大鼠子宫内膜异位症的治疗作用。减少子宫内膜植入物体积的程度与达那唑（100 mg/kg/天，p.o.）相同。同时，地诺孕素改善了子宫内膜植入物诱导的免疫系统改变：即，它增加了腹腔液细胞和脾细胞的自然杀伤活性，减少了腹腔液细胞的数量，并减少了腹腔巨噬细胞产生的白细胞介素-1 β。相比之下，达那唑（100 mg/kg/天，p.o.）和布舍瑞林（30 μ g/kg/天，s.c.）没有这些免疫学效应。此外，地诺孕素（0.1 mg/kg/天）与布舍瑞林（0.3 μ g/kg/天）联合给药可抑制布舍瑞林单独给药诱导的骨矿物质丢失，对子宫内膜种植体的影响未降低。地诺孕素的体外研究显示，由于蛋白激酶C活性的抑制，加上一个部分progestive effect.Conclusions：地诺孕素对大鼠子宫内膜细胞的抗增殖作用似乎是一个有效的代理与达那唑和GnRH激动剂目前可用于治疗子宫内膜异位症的作用机制不同。
Objective: Dienogest, a synthetic steroid with progestational activity, is used as a component of oral contraceptives and is currently being evaluated clinically for the treatment of endometriosis. Thee present study was conducted to confirm the effects of dienogest on experimental endometriosis in rats and to elucidate its mechanism of action.Design: Experimental endometriosis induced by autotransplantation of endometrium in rats.Methods: Endometrial implants, immune system, and bone mineral were investigated after 3 weeks of medication.Results: Dienogest (0.1-1mg/kg per day, p.o.) reduced the endometrial implant volume to the same extent as danazol (100 mg/kg per day, p.o.). Simultaneously, dienogest ameliorated the endometrial implant-induced alterations of the immune system: i.e. it increased the natural killer activity of peritoneal fluid cells and splenic cells, decreased the number of peritoneal fluid cells, and decreased interleukin-1 beta production by peritoneal macrophages. In contrast, danazol (100 mg/kg per day, p.o.) and buserelin (30 mu g/kg per day, s.c.) had none of these immunologic effects. Additionally, combined administration of dienogest (0.1 mg/kg per day) plus buserelin (0.3 mu g/kg per day) suppressed the bone mineral loss induced by buserelin alone, with no reduction of the effect on endometrial implants. In vitro studies on dienogest revealed an antiproliferative effect on rat endometrial cells due to inhibition of protein kinase C activity plus a partial progestational effect.Conclusions: Dienogest appears to be a potent agent with mechanisms of action different from those of danazol and GnRH agonists currently available for the treatment of endometriosis.