CONTROL OF ADH SECRETION AND METABOLISM

有重要的性别相关的生理和病理生理 心血管和体液调节的差异。 因此 例如，高血压的发病率和死亡率， 男性心血管疾病的发病率高于绝经前女性;以及 经前综合症的症状之一是水潴留。 由于加压素（AVP）参与心血管和机体的调节， 流体稳态，AVP可能参与这些性别相关的差异。 事实上，我们最近已经证明，AVP释放的控制是 两性异形 另外，我们有证据表明 去甲肾上腺素能、胆碱能和血管紧张素能通路在 AVP释放的性二态控制。 很可能伽马射线- 氨基丁酸（GABA）介导的途径也参与控制 AVP的释放，有理由表明，这种行动的GABA可能 受到性腺类固醇激素的调节。 因此，我们建议， 性腺类固醇激素在控制AVP释放中起关键作用 通过调节与此相关的神经递质的作用， 控制 提出了实验来表征的功能， 去甲肾上腺素能、GABA能、胆碱能和血管紧张素能途径 性二态控制AVP的释放，以确定性质的 这些神经递质与性腺类固醇激素的相互作用， 并确定这些相互作用发生的大脑部位。 因此，所提出的实验旨在提供对 AVP的性二态控制的中枢机制 在个体性腺之间相互作用的背景下释放 类固醇激素和特定的神经递质。 反过来，这项工作应该 促进我们对有助于实现这些目标的核心机制的理解， 与性别有关的生理和病理生理差异， 心血管和体液调节。

There are important gender-related physiological and pathophysiological differences in cardiovascular and body fluid regulation. Thus, for example, the incidence of hypertension and the mortality due to cardiovascular disease are higher in men than in pre-menopausal women; and one of the symptoms of the Premenstrual Syndrome is water retention. Because vasopressin (AVP) participates in both cardiovascular and body fluid homeostasis, AVP may be involved in these gender-related differences. Indeed, we have recently demonstrated that the control of AVP release is sexually dimorphic. In addition, we have obtained evidence that central noradrenergic, cholinergic, and angiotensinergic pathways play a role in the sexually dimorphic control of AVP release. It is likely that gamma- aminobutyric acid (GABA)-mediated pathways also participate in the control of AVP release, and there is reason to suggest that this action of GABA may be modulated by th gonadal steroid hormones. We propose, therefore, that the gonadal steroid hormones play a key role in the control of AVP release by modulating the actions of neurotransmitters that are involved in this control. Experiments are proposed to characterize the function of noradrenergic, GABAergic, cholinergic, and angiotensinergic pathways in the sexual dimorphic control of AVP release, to define the nature of the interactions of these neurotransmitters with the gonadal steroid hormones, and to identify the brain sites where these interactions take place. Thus, the proposed experiments are aimed at providing an understanding of the central mechanisms that underlie the sexually dimorphic control of AVP release in the context of interactions between the individual gonadal steroid hormones and specific neurotransmitters. In turn this work should further our understanding of the central mechanisms that contribute to the gender-related physiological and pathophysiological differences in cardiovascular and body fluid regulation.