Oestrogenic regulation of brain angiotensinogen

Oestrogens are now recognized as playing a regulatory role on components of the systemic renin-angiotensin system, such as its precursor, angiotensinogen (AGT). In the brain, this role is poorly understood. The aim of this study was to investigate the influence of oestrogens on brain AGT of female rats at different stages of the oestrous cycle, in pregnancy and following ovariectomy with and without hormone replacement. AGT content of different brain regions was also studied in male rats treated with oestrogens. The brain was divided into five regions: cortex, cerebellum, brainstem, midbrain and thalamus/hypothalamus, and AGT was measured by direct radioimmunoassay using a highly specific AGT antibody. Cyclical fluctuations in AGT content were observed in all regions except the cerebellum over the course of the 4-day oestrous cycle, with peak concentrations at estrus and lowest concentrations at metestrus. Following ovariectomy, brain AGT was significantly decreased in the thalamic/hypothalamic region, an effect that was reversed by oestrogen-replacement. In pregnant rats, AGT contents were elevated in the brainstem region. Oestrogen treatment of male rats induced significant increases in AGT concentrations in all areas except the cortex. In summary, these results show that oestradiol has actions on brain AGT that are region-specific and dependent on the particular physiological and reproductive context. Moreover, the changes in AGT concentrations in the oestrous cycle suggest the involvement of other factors besides oestrogen. Finally, this study supports the view that the brain renin-angiotensin system has a broad role in oestrogen-modulated brain functions beyond those specific to the hypothalamic-pituitary-ovarian axis.