Role of Estrogen Receptors and Neurohypophyseal Gene Expression in Vasopressin Release in a Model of Dilutional Hyponatremia

目的：低钠血症是最常见的电解质紊乱，2006年治疗费用较高。 据估计，美国每年的低钠血症约为16-36亿美元。不适当的加压素 分泌物是与肝脏和心力衰竭相关的稀释性低钠血症的主要原因。我们的 以往的研究也表明，在雄性BDL大鼠中，BDNF-TrkB信号在SON中 促进AVP和Copeptin(AVP 1-3的临床替代物)的持续释放，以及 低钠血症4。然而，对性别差异在低钠血症中的作用知之甚少。我们的 数据显示，雌性BDL大鼠不会出现低钠血症或AVP释放增加。取而代之的是 雌性BDL大鼠表现出催产素6释放增加。我们的研究结果还表明， BDL对神经垂体激素的影响可能是性二态的。我们的中心假设是 下丘脑-神经垂体系统(HNS)中的内质网至少在一定程度上与性行为有关 在稀释性低钠血症的BDL模型中看到的差异。 我们的假设将通过以下具体目标进行检验： 目标1将确定雌激素受体在下丘脑-神经垂体中的作用 稀释性低钠血症模型中神经元对性别的差异 目标2将确定可能有助于潜在性别的SON基因表达的差异 稀释性低钠血症模型中AVP释放的差异 好处：这些实验将解决我们对 神经植物功能与低钠血症的发病机制。这些研究的结果 实验可能会改变不适当的加压素释放的研究方式，并 在临床上概念化。

Purpose: Hyponatremia is the most common electrolyte disorder and in 2006 the cost of treating hyponatremia in the US was estimated to be $1.6-$3.6 billion per year. Inappropriate vasopressin secretion is the major cause of dilutional hyponatremia associated with liver and heart failure. Our previous studies have also shown that, in male BDL rats, BDNF-TrkB signaling in the SON contributes sustained AVP and copeptin (a clinical surrogate for AVP 1-3) release, and hyponatremia 4. However, little is known about the role of sex differences in hyponatremia5. Our data show that female BDL rats do not develop hyponatremia or increased AVP release6. Instead female BDL rats show increased release of oxytocin6 . Our findings also suggest that the effects of BDL on neurohypophyseal hormones may be sexually dimorphic. Our central hypothesis is that ER in the hypothalamo-neurohypophyseal system (HNS) contribute, at least in part, to sex differences seen in the BDL model of dilutional hyponatremia. Our hypotheses will be tested with the following Specific Aims: Aim 1 will define the contributions of estrogen receptors in hypothalamo-neurohypophyseal neurons to sex differences in a model of dilutional hyponatremia Aim 2 will determine differences in SON gene expression that may contribute to underlying sex differences in AVP release in a model of dilutional hyponatremia Benefit: These experiments will address an existing gap in our understanding of neurophypophyseal function and the pathogenesis of hyponatremia. The findings of these experiments could potentially alter the way that inappropriate vasopressin release is studied and conceptualized clinically.