Role of Estrogen in Stimulated Water Intake

描述(申请人提供)：体液平衡由包括水摄入量在内的荷尔蒙和行为综合机制维持。关于这一主题的大部分研究都是在雄性动物模型上进行的。然而，越来越清楚的是，女性对脱水的反应与男性不同。事实上，人们普遍同意雌激素调节水分摄入量以应对脱水。尽管有这一普遍的共识，但关于雌激素在应对特定脱水挑战中的作用，仍有相互矛盾的发现。此外，荷尔蒙调节的方法学差异使得这些研究难以评估。更重要的是，人们对雌激素对水摄入量影响的神经机制和中枢通路知之甚少。大多数研究这一问题的研究都使用了血管紧张素II的中枢给药来刺激水的摄入。尽管这些研究的结果提供了令人信服的证据，证明雌激素/血管紧张素II在控制摄水量方面存在中枢相互作用，但目前尚不清楚这种相互作用是否涉及更多的水摄入生理刺激。因此，本提案的目标是区分雌激素对饮酒行为的影响，并确定激素影响雌性啮齿动物口渴的机制。通过这样做，我们将检验总体假设，即雌激素和血管紧张素II之间的中枢相互作用是雌激素对生理刺激的水摄入量产生影响的基础。

DESCRIPTION (provided by applicant): Body fluid homeostasis is maintained by integrated hormonal and behavioral mechanisms, including water intake. The majority of research on this topic has been done in male animal models. However, it is becoming increasingly clear that females respond differently to dehydration than do males. In fact, there is general agreement that estrogen modulates water intake in response to dehydration. Despite this general agreement, there are conflicting findings about the role of estrogen in the responses to specific dehydrational challenges. In addition, methodological differences in hormonal manipulations make these studies difficult to assess. More importantly, very little is known about the neural mechanisms and central pathways underlying the effect of estrogen on water intake. Most studies that have examined this issue have used central administration of angiotensin II to stimulate water intake. Although results from these studies provide compelling evidence for a central estrogen/angiotensin II interaction in the control of water intake, it is unclear whether such an interaction is involved in more physiological stimuli for water intake. Accordingly, the goals of the present proposal are to distinguish estrogen effects on drinking behavior and ascertain the mechanism by which the hormone affects the thirst of female rodents. By doing so, we will test the overall hypothesis that central interactions between estrogen and angiotensin II underlie the effect of estrogen on physiologically stimulated water intake.