REGULATION OF VASOPRESSIN MESSENGER RNA DURING AGING

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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.