The role of estrogen receptors in cardiovascular function

雌激素是一种对心脏有复杂影响的激素家族。部分复杂性可归因于三种雌激素受体（ER）（ER-α、ER-β和GPR 30）的存在。在某些情况下，这些受体的激活可以产生相反的功能效应。我们的研究计划的目标是确定每个ER如何影响心脏功能，并确定其细胞内的作用机制。 男性和女性的心脏功能不同，这些差异的原因可能是ER控制心脏的方式。我们的第一个目标是确定雄性和雌性小鼠如何响应ER激活，并确定细胞内的作用机制。这些实验通过超声心动图观察整个心脏功能，并研究每个ER诱导的分子变化。这些研究将深入了解雄性和雌性之间以及雌性在整个发情周期中ER生理学的差异。 植物雌激素是植物性化合物，在动物饮食中越来越普遍。高达25%的人类婴儿被喂食富含植物雌激素的大豆配方奶粉，许多宠物食品都补充了大豆产品。最后，世界上绝大多数大豆作物都被加工并用作食用动物的饲料。尽管植物雌激素的消费量广泛且不断增加，但对这些化合物对心脏生理学的影响或其作用机制知之甚少。植物雌激素的作用可能与动物雌激素相反，提示不同的作用机制。我们的第二个目标是通过超声心动图和心导管检查研究膳食植物雌激素对整个心脏功能的影响，并通过检查细胞内信号传导途径和心肌细胞修饰来确定细胞内作用机制。这些研究将提供有关植物雌激素对心脏生理学影响的信息，以及这些化合物对实验室和食用动物以及人类的潜在影响。

Estrogens are a family of hormones that have complex effects on the heart. Part of the complexity can be attributed to the existence of three estrogen receptors (ER) (ER-alpha, ER-beta, and GPR30). In some cases the activation of these receptors can produce opposing functional effects. The objectives of our research program are to determine the how each ER affects heart function, and to determine their intracellular mechanisms of action. Heart function differs between males and females, and a reason for these differences may be the way ER control the heart. Our first objective is to determine how male and female mice respond to ER activation, and determine the intracellular mechanisms of action. These experiments look at whole heart function by echocardiography, and investigate the molecular changes induced by each ER. These studies will provide insight into differences in ER physiology between males and females, and in females throughout the estrus cycle. Phytoestrogens are plant-based compounds that are becoming increasingly prevalent in animal diets. Up to 25% of human infants are fed soy based formula that is rich in phytoestrogens, and many pet foods are supplemented with soy products. Finally, the vast majority of the world's soybean crops are processed and used as feed for food animals. Despite the widespread and increasing consumption of phytoestrogens by a number of animal species, little is known about the effects of these compounds on cardiac physiology, or their mechanisms of action. The effects of phytoestrogens can be opposite to that of animal estrogens, suggesting distinct mechanisms of action. Our second objective is to investigate the impact of dietary phytoestrogens on whole heart function by echocardiography and cardiac catheterization, and to identify intracellular mechanisms of action by examining intracellular signaling pathways and cardiac muscle cell modifications. These studies will provide information about the effects of phytoestrogens on heart physiology, and the potential impact these compounds have on laboratory and food animals, as well as humans.