Otto Christiane, Schkoldow Jenny, Krahl Elisabeth, Fuchs Iris, Ulbrich Hannes-Friedrich
Therapeutic Research Group Oncology and Gynecological Therapy;
Exp Ther Med. 2012 Mar;3(3):410-414. doi: 10.3892/etm.2011.425. Epub 2011 Dec 20.
Endometriosis is a chronic, estrogen-dependent disease characterized by the presence of ectopic endometrium either in the pelvic cavity (endometriosis externa) or within the uterus (endometriosis interna, adenomyosis). Key symptoms are pelvic pain, dysmenorrhea and infertility. Established rodent animal models used for drug research in endometriosis have certain limitations. Since rodents do not menstruate, they cannot develop endometriosis externa spontaneously, but they suffer from endometriosis interna. There is growing evidence that human endometriosis externa and interna represent two faces of the same disease. Both are estrogen-dependent and respond to similar treatment paradigms. Here, we addressed the question whether a murine endometriosis interna model may also be suitable for the characterization of drugs employed in human endometriosis. We examined the effects of danazol, Faslodex and cetrorelix in SHN mice that developed endometriosis interna after pituitary grafting. The GnRH antagonist cetrorelix and the estrogen receptor antagonist Faslodex, which negatively interfered with estrogen-mediated signaling, completely inhibited endometriosis interna, whereas danazol, an androgenic progestin, showed significant therapeutic activity in the majority of SHN mice. We conclude that this murine endometriosis interna model may be a valuable complement to established endometriosis externa models to support drug research in human endometriosis.
子宫内膜异位症是一种慢性雌激素依赖性疾病，其特征是在盆腔腔（外在性子宫内膜异位症）或子宫内（内在性子宫内膜异位症，子宫腺肌病）存在异位子宫内膜。主要症状是盆腔疼痛、痛经和不孕。用于子宫内膜异位症药物研究的现有啮齿动物模型存在一定局限性。由于啮齿动物不会月经来潮，它们不能自发发生外在性子宫内膜异位症，但会患内在性子宫内膜异位症。越来越多的证据表明，人类外在性子宫内膜异位症和内在性子宫内膜异位症是同一疾病的两个方面。两者均为雌激素依赖性，且对相似的治疗模式有反应。在此，我们探讨了小鼠内在性子宫内膜异位症模型是否也适用于表征用于人类子宫内膜异位症的药物这一问题。我们研究了达那唑、氟维司群和西曲瑞克对垂体移植后发生内在性子宫内膜异位症的SHN小鼠的影响。GnRH拮抗剂西曲瑞克和雌激素受体拮抗剂氟维司群对雌激素介导的信号传导产生负面干扰，完全抑制了内在性子宫内膜异位症，而雄激素类孕激素达那唑在大多数SHN小鼠中显示出显著的治疗活性。我们得出结论，这种小鼠内在性子宫内膜异位症模型可能是现有外在性子宫内膜异位症模型的有价值补充，以支持人类子宫内膜异位症的药物研究。
