CONTROL OF ADH SECRETION AND METABOLISM

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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.