Letrozole-induced polycystic ovaries in the rat: A new model for cystic ovarian disease

Letrozole-induced polycystic ovaries in the rat: A new model for cystic ovarian disease
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DOI:
10.1016/j.arcmed.2003.10.005
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发表时间:
2004-03-01
影响因子:
7.7
通讯作者:
Demir, N
Demir, N
中科院分区:
医学4区
文献类型:
--
作者:
Kafali, H;Iriadam, M;Demir, N

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背景资料。我们的目的是利用非甾体芳香酶抑制剂来曲唑建立一种新的研究多囊卵巢的动物模型。将34只大鼠分为4组,其中对照组10只,仅给予赋形剂(1%羧甲基纤维素水溶液[CMC])灌胃,每日1次(P.O.)3个处理组,每组8只,分别给予来曲唑0.1、0.5或1 mg/kg灌胃。溶于1%CMC(2毫升/公斤),每日一次。疗程为21天。在此期间,每天收集阴道涂片以确定发情周期。在最后一次给药的第二天,大鼠被处死;然后切除子宫和卵巢并称重。检测血清激素水平和卵巢组织学变化。与对照组相比,研究组卵巢包膜下囊肿和包膜增厚的发生率高,黄体形成不完全,黄体数目减少。来曲唑治疗对卵巢重量没有明显影响,但对子宫重量有剂量依赖性的抑制作用。虽然血清雌二醇和孕酮水平以剂量依赖的方式降低,但睾酮水平和黄体生成素水平升高。高剂量来曲唑(0.5 mg/kg和1.0 mg/kg)血清促卵泡激素(FSH)水平显著升高,而低剂量来曲唑(0.1 mg/kg)略有下降。尽管对于多囊卵巢或多囊卵巢综合征(PCOS)的整体研究来说,这并不是一个完全令人信服的模型,但这个动物模型在几个方面与人类多囊卵巢综合征相似。(C)2004年管理和社会保障制度。由爱思唯尔公司出版。
Background. Our objective was to develop a new animal model for the study of polycystic ovaries by using the non-steroidal aromatase inhibitor, letrozole.Methods. Thirty four rats were divided into four groups, including a control group of 10 rats that received vehicle only (1% aqueous solution of carboxmethlycellulose [CMC]) once daily orally (p.o.) and three treatment groups of eight rats each that were administered letrozole at concentrations of 0.1 or 0.5 or 1 mg/kg p.o. dissolved in 1% CMC (2 mL/ kg) once daily. The treatment period was 21 days. During this period, vaginal smears were collected daily for estrus cycle determination. On the day subsequent to last letrozole dose administration, rats were killed; uteri and ovaries were then excised and weighed. Serum hormone levels and histologic changes in ovaries were examined.Results. When compared to control group, ovaries from study groups showed high incidence of subcapsular ovarian cyst and capsular thickening together with incomplete luteinization and decreased number of corpora lutea. Letrozole treatment brought about dose-dependent suppression of uterine weight despite having no significant effect on ovarian weight. Although serum estradiol and progesterone levels were reduced in a dose-dependent manner, testosterone levels were elevated as were levels of luteinizing hormone (LH). Serum follicle-stimulating hormone (FSH) levels were markedly increased at higher doses of letrozole (0.5 and 1.0 mg/kg), contrary to low dose of letrozole (0.1 mg/kg) at which slight decrease was observed.Conclusions. Despite the fact that this is not a fully convincing model for the study of polycystic ovaries or of polycystic ovary syndrome (PCOS) as a whole, this animal model in several ways is similar to the human polycystic ovary syndrome. (C) 2004 IMSS. Published by Elsevier Inc.