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

稀释性低钠血症模型中雌激素受体和神经垂体基因表达在加压素释放中的作用

• 批准号: 10608943
• 负责人: DIANNA HUYEN-TRAM NGUYEN
• 金额: $ 3.37万
• 依托单位: UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10608943
• 关键词: Acute; Animal Model; Arginine; Body Fluids; Body Water; Brain-Derived Neurotrophic Factor; Cardiovascular system; Central Nervous System; Chronic Disease; Circulation; Cirrhosis; Clinical; Congestive Heart Failure; Data; Development; ESR1 gene; Electrolyte Disorder; Estrogen Receptor beta; Estrogen Receptors; Female; Fluid Balance; Fostering; Fulvestrant; Functional disorder; GPER gene; Gene Expression; Goals; Heart failure; Hormones; Hospitals; Hyponatremia; Hypothalamic structure; Infusion procedures; Injury; Kidney; Knowledge; Ligation; Liquid substance; Literature; Liver Cirrhosis; Liver Failure; Modeling; Neurons; Osmoregulation; Outcome; Oxytocin; Pathogenesis; Patients; Peripheral; Physiological; Posterior Pituitary Hormones; Prognosis; Rattus; Regulation; Research; Resources; Risk Factors; Role; Sex Differences; Signal Transduction; Sodium; Spinal cord injury; Subarachnoid Hemorrhage; Surrogate Markers; System; Testing; Therapeutic; Trauma; United States; V2 Receptors; Vasopressins; Water; antagonist; bile duct; clinical practice; cost; defined contribution; dilutional hyponatremia; experimental study; insight; magnocellular; male; mortality; new therapeutic target; novel; novel therapeutic intervention; older patient; paraventricular nucleus; patient population; sex; sexual dimorphism; supraoptic nucleus; transcriptomics

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.

目的：低钠血症是2006年最常见的电解质紊乱和最昂贵的治疗方法