REGULATION OF VASOPRESSIN MESSENGER RNA DURING AGING

水平衡失调是老年人常见的疾病 受试者包括低钠血症、脱水和口渴减轻。研究 试图确定这些机制的基础上， 异常 该实验室先前的研究表明， 血浆加压素（VP）浓度的正常增加， 下丘脑VP mRNA含量和大小与长时间 脱水在老年雄性大鼠中不存在。 本提案的目的是 研究造成这些缺陷的机制，并确定 如果在老年雌性大鼠中观察到类似的异常。两个不同 将检验假设：1）脱水不能增加VP 老年雄性大鼠中的mRNA发生继发于低循环水平的 性腺类固醇，特别是睾酮;和2） 脱水增加VP mRNA在老年雄性大鼠发生继发于 与年龄相关的糖皮质激素循环水平升高。的 第一个假设提出了潜在的性别差异的问题， 衰老对VP mRNA调控的影响。的具体目标 项目有： 1.确定老年男性Fisher 344是否需要睾酮 大鼠将纠正VP释放和下丘脑VP mRNA的缺陷 先前在慢性脱水老年雄性大鼠中观察到的含量。 2.为了确定是否与衰老相关的睾丸激素分泌减少 干扰脱水诱导的VP mRNA含量的增加，但不 VP mRNA的大小，在VP释放不足的年龄之前， 观察这些研究可能会提供洞察力的重要性， VP mRNA含量相对于大小增加，以维持持续VP 慢性脱水时的分泌物 3.为了确定在衰老对老年人的影响方面是否存在性别差异， 脱水引起VP释放和下丘脑VP mRNA大小增加 和含量。 4.确定糖皮质激素是否导致VP释放不足 以及VP mRNA的含量和大小。

Abnormalities of water balance are commonly encountered in elderly human subjects including hyponatremia, dehydration, and reduced thirst. Studies are proposed to attempt to identify the mechanisms underlying these abnormalities. Prior studies from this laboratory have demonstrated that the normal increases in plasma vasopressin (VP) concentration and hypothalamic VP mRNA content and size associated with prolonged dehydration are absent in aged male rats. The goal of this proposal is to study the mechanisms responsible for these deficiencies, and to determine if similar abnormalities are observed in aged female rats. Two distinct hypotheses will be tested: 1) that failure of dehydration to increase VP mRNA in aged male rats occurs secondary to the low circulating levels of gonadal steroids, particularly testosterone; and 2) that failure of dehydration to increase VP mRNA in aged male rats occurs secondary to the aging-associated elevation in circulating levels of glucocorticoids. The first hypothesis raises the issue of potential gender differences in the effect of aging on the regulation of VP mRNA. The specific goals of the project are: 1. To determine if testosterone administration to aged male Fisher 344 rats will rectify the deficits in VP release and hypothalamic VP mRNA content previously observed in chronically dehydrated aged male rats. 2. To determine if aging-associated decreases in testosterone production interfere with dehydration induced increases in VP mRNA content, but not size of VP mRNA, prior to the age at which deficits in VP release are observed. These studies may provide insights into the importance of increases in VP mRNA content versus size for maintenance of sustained VP secretion during chronic dehydration. 3. To determine if gender differences exist in the effect of aging on dehydration induced increases in VP release and hypothalamic VP mRNA size and content in Fisher 344 rats. 4. To determine if glucocorticoids contribute to the deficit in VP release and VP mRNA content and size in chronically dehydrated aged rats.