他莫西芬对大鼠血清雌孕激素及子宫雌孕激素受体的影响

Effect of tamoxifen on serum estrogen and progesterone level as well as uterus estrogen and progesterone receptor expression in rats

关键词:  他莫西芬  子宫内膜  雌激素受体  孕激素受体

Key words:  tamoxifen  uterus  estrogen receptor  progesterone receptor

摘要:

目的　探讨他莫西芬（tamoxifen,TAM）对大鼠血清雌、孕激素分泌水平以及对大鼠子宫雌、孕激素受体（ERα、ERβ、PR）表达状况的影响。　方法　40只成年雌性SD大鼠随机分为4组：假手术组（SHAM组）、假手术+TAM组(SHAM+TAM组)、去势手术组（OVX组）、去势手术+TAM组（OVX+TAM组），每组10只。假手术组在找到卵巢后即分层缝合，关闭腹腔；去势手术组切除双侧卵巢建立OVX动物模型。SHAM+TAM和OVX+TAM组每日灌胃TAM；SHAM和OVX组给予等量蒸馏水，连续给药28 d。给药前后应用放射免疫分析法检测血清雌、孕激素分泌水平，实验结束处死大鼠取子宫，称量子宫重量，计算子宫系数，Western blot方法检测子宫的ERα，ERβ和PR的表达水平。　结果　与SHAM组相比，SHAM+TAM组大鼠子宫湿重显著降低（P＜0.01），子宫系数降低了47%。与OVX组相比，OVX+TAM组大鼠子宫湿重显著增加（P＜0.05），子宫系数是OVX组的1.87倍。SHAM+TAM组雌激素和孕激素水平均显著低于SHAM组，P<0.05。OVX+TAM组雌激素水平显著高于OVX组，而孕激素水平则极显著低于OVX组。与OVX组相比，OVX+TAM组ERβ的表达显著降低（P<0.05），SHAM组PR的表达量显著降低（P<0.05）。OVX+TAM组的PR水平显著高于OVX组（P<0.05），并与SHAM组水平相当（P>0.05)。　结论　TAM在不同雌激素水平条件下，对性激素分泌的影响是不同的。TAM在大鼠子宫内膜有雌激素样作用。TAM导致子宫内膜病变的机制可能与其雌激素样作用以及对性激素受体的调节有关。

Abstract:

Objective　 To study the effects of tamoxifen on the levels of serum estrogen and progesterone as well as the expression of estrogen receptor (ERα, ERβ) and progesterone receptor (PR) in uterus in rats. 　Methods Forty female SD rats were randomly and evenly assigned into four groups: sham operated group (SHAM), sham operated plus tamoxifen (SHAM+TAM), bilaterally ovariectomized group (OVX), and bilaterally ovariectomized plus tamoxifen group (OVX+TAM). All animals were daily oral administrated with tamoxifen or solvent control for 28 days. Serum estrogen and progesterone levels were measured before and after tamoxifen administration. After the experiment, all the rats were sacrificed for uterus weighting, and uterus coefficient were calculated. The expression levels of ERα, ERβ, and PR in uterus were detected by Western blot assay. 　Results Tamoxifen significantly increased the serum estrogen levels in OVX rats, but decreased the serum estrogen levels in SHAM rats. In both OVX and SHAM rats, tamoxifen decreased the serum progesterone levels. Tamoxifen significantly decreased the uterus weight and uterus coefficient in SHAM rats, but increased the uterus weight and uterus coefficient in OVX rats. There was no significant effect of tamoxifen on ERα, while tamoxifen administration down-regulated the expression of ERβ and up-regulated the expression of PR. 　Conclusion Estrogen level could influence the effect of tomaxifen on sex hormone secretion. Tamoxifen could be associated with the pathogenesis of endometrium by tamoxifen changing hormone receptor expression.