Katsuki Y, Takano Y, Futamura Y, Shibutani Y, Aoki D, Udagawa Y, Nozawa S
Toxicology Laboratory, Mochida Pharmaceutical Co. Ltd, Fujieda, Shizuoka, Japan.
Eur J Endocrinol. 1998 Feb;138(2):216-26. doi: 10.1530/eje.0.1380216.
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. The present study was conducted to confirm the effects of dienogest on experimental endometriosis in rats and to elucidate its mechanism of action.
Experimental endometriosis induced by autotransplantation of endometrium in rats.
Endometrial implants, immune system, and bone mineral were investigated after 3 weeks of medication.
Dienogest (0.1-1 mg/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-1beta production by peritoneal macrophages. In contrast, danazol (100 mg/kg per day, p.o.) and buserelin (30 microg/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 microg/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.
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.
地诺孕素是一种具有孕激素活性的合成甾体，用作口服避孕药的成分，目前正在进行治疗子宫内膜异位症的临床评估。本研究旨在证实地诺孕素对大鼠实验性子宫内膜异位症的作用，并阐明其作用机制。
通过大鼠自体移植子宫内膜诱导实验性子宫内膜异位症。
用药3周后研究子宫内膜植入物、免疫系统和骨矿物质。
地诺孕素（每天0.1 - 1毫克/千克，口服）使子宫内膜植入物体积减小的程度与达那唑（每天100毫克/千克，口服）相同。同时，地诺孕素改善了子宫内膜植入物引起的免疫系统改变：即增加了腹腔液细胞和脾细胞的自然杀伤活性，减少了腹腔液细胞数量，并降低了腹腔巨噬细胞产生白细胞介素-1β的水平。相比之下，达那唑（每天100毫克/千克，口服）和布舍瑞林（每天30微克/千克，皮下注射）没有这些免疫作用。此外，地诺孕素（每天0.1毫克/千克）加布舍瑞林（每天0.3微克/千克）联合给药抑制了单独使用布舍瑞林引起的骨矿物质流失，且对子宫内膜植入物的作用没有减弱。地诺孕素的体外研究显示，由于抑制蛋白激酶C活性，其对大鼠子宫内膜细胞具有抗增殖作用，并具有部分孕激素作用。
地诺孕素似乎是一种有效的药物，其作用机制不同于目前可用于治疗子宫内膜异位症的达那唑和促性腺激素释放激素激动剂。
