Angiotensin-estrogen central interaction: localization and mechanism

Abstract

Intracerebroventricular (ICVT) administration of estradiol benzoate (EB) to ovariectomized female rats decreased drinking and pressor responses to central injections of angiotensin II (AII). Estrogen treatment does not have this effect in male rats. As EB given ICVT reaches many brain areas, the site of action of EB was localized using crystalline implants of EB in the medial preoptic area or the ventromedial nucleus of the hypothalamus. These areas were chosen as they have a high density of estrogen receptors. Only medial preoptic area application of estrogen decreased angiotensin II-induced drinking. Angiotensin receptor binding was examined in homogenates from different brain regions to determine if the mechanism through which estrogen decreases central responses to AII involves altered receptor function. Systemic EB did not affect AII receptor binding in several brain regions but binding was decreased in homogenates from the preoptic area and septum-thalamus blocks which encompassed structures (median preoptic nucleus, organum vasculosum, and subfornical organ) implicated in central actions of AII. The sex specificity of the effect of estrogen was dependent on sexual differentiation of the brain. Manipulation of the neonatal hormone environment, which alters this brain differentiation, also altered the characteristic responses of the two sexes to estrogen. Neonatal androgenization of females, which causes masculinization and defeminization, resulted in animals which as adults no longer responded to EB with decreased drinking. On the other hand, preventing the development of a male brain by neonatal castration produced animals which as adults tended to decrease their drinking following estrogen. In summary, this study found that EB acts in the preoptic area to depress AII-induced responses by a site specific modulation of central AII receptors. Alteration of early brain development changed the responses of the two sexes to estrogen, perhaps by altering sexual differentiation of the preoptic area.