雌激素对大鼠心脏雌激素受体α和β表达的影响

EFFECTS OF ESTROGEN ON ESTROGEN RECEPTOR α AND β IN RAT HEART

目的研究雌激素受体(ER)α和β在新生、成年和卵巢切除大鼠心脏的表达.方法采用半定量逆转录聚合酶链反应(RT-PCR)和Western blot方法,分析新生和成年大鼠心脏各部的ERα和β mRNA及ER蛋白质的表达,探讨不同剂量的17β-雌二醇对卵巢切除大鼠心脏ERα和β mRNA、ER蛋白质的表达调控及对心房、心室重量和它们与体重比变化的影响.结果ERα mRNA在新生大鼠心脏各部表达较低,而成年大鼠心脏各部ERαmRNA的转录水平提高3～20倍,这种差别体现在ERα蛋白质的表达水平不同.反之新生大鼠心脏ERβ mRNA表达水平较高,而成年大鼠心脏ERβmRNA的表达降低2～7倍.卵巢切除减少成年大鼠心房ERα mRNA和蛋白质的表达,减轻心房重量及心房/体重比;17β-雌二醇替代却能反转这些改变,同时随着血浆17β-雌二醇水平的增高,这种影响在一定程度上呈剂量依赖关系.卵巢切除和17β-雌二醇替代并不改变心脏和心室/体重比,也不影响ERβmRNA的表达.结论雌激素受体α和β在新生和成年大鼠心脏的表达存在差别,ERβ可能在大鼠心脏的发育过程中起重要作用,ERα是雌激素对成年大鼠心脏调控的优势受体;雌激素的主要靶器官是心房,且通过其受体的介导促进心房肌细胞的增生.

Objective To study estrogen receptor （ER） α and β expression in the newborn and adult rats,and effect of estrogen on ERa and ERβ in ovarieetomized rat heart.Methods By RT-PCR and Western blot analysis,changes in ERa and ERβ in newborn and adult rat heart chambers were investigated, and subsequently, the effect of 17βestradiol deficit and supplementation on ERα and ERβ, and heart chamber wieght and ratio to body weight in ovarieetomized rats were evaluated. Results ERα mRNA was lower in all heart chambers of newborn rats, but was elevated by 3-to 20-fold in the atria and ventricles of adult rats, these differences were efficiently translated into 67 kD ERa protein. Inversely, ERβ mRNA expressed in the heart chambers of newborn rats was higher, and was dramatically decreased by 2-to 7-fold in all heart chambers of adult rats. In adult rats, ovarieetomy decreased atrial ERα mRNA and ERa protein expression, and the atrial weight and atria/body weight ratio. Treatment with 17β- estradiol in ovarieetomized rats reversed these changes; meanwhile these changes showed the dose-dependent relation to some extent along with the increment of 17β-estradiol dosage, but ovarieetomy and treatment with 17β-estradiol did not alter the atria ERβ mRNA expression, and the heart, ventricle ratio to body weight. Conclusion ERs expression is different between the newborn and adult rat heart, ERβ may play an important role than ERa in the development of the rat heart, ERα high expression suggests that it funetions as a predominant estrogenie mediator in adult heart. Estrogen mainly targets the atria; and aetivates atrio-myoeyte proliferation via ERa mediated mechanism.