Endogenous aldosterone and corticosterone in brain cell nuclei of adrenal-intact rats: regional distribution and effects of physiological variations in serum steroids

In vivo brain uptake of labeled aldosterone (ALD) and corticosterone (CORT) in adrenalectomized (ADX) rats indicates a strong cell-nuclear localization of both hormones, predominantly in the hippocampus. The primarily limbic concentration of these hormones is also supported by in vitro assays of ALD and CORT binding in cytosol from ADX rats. However, assays of binding in tissues from ADX rats often fail to account for the normal competition of assorted corticosteroids for binding sites in the adrenal-intact subject. Because the binding affinity of corticoid receptors for CORT is greater than, or equivalent to that for ALD, and plasma concentrations of CORT exceed ALD levels, it is possible that ALD is not actually concentrated by brain cell-nuclei in the normal, adrenal-intact subject. Moreover, description of the brain's in vivo regional uptake of ALD or CORT in ADX rats may reflect labeling of heterogenous binding sites by the single corticosteroid ligand ([³H]ALD or [³H]CORT) under investigation. Research using subcellular fractionation and radioimmunoassay (RIA) has demonstrated the presence of endogenously secreted CORT in brain cell nuclei of adrenal-intact rats, and confirmed the principally limbic localization of endogenous CORT in the brain. In the present study, subcellular fractionation and RIA were employed to determine whether endogenously secreted ALD is concentrated by cell nuclei of the brain in adrenal-intact rats, and to assess the regional variation in the brain's cell-nuclear uptake of endogenously secreted ALD. Cell-nuclear CORT levels were also measured in this experiment to assess the possible competition between ALD and CORT for brain cell-nuclear uptake. Circadian rhythms. stress and dietary sodium were utilized in this study to induce physiological variations in serum ALD and CORT. Endogenous ALD was found in the nuclear fraction of all brain tissues tested, indicating that ALD is bound and translocated to brain cell nuclei in the presence of normal corticosteroid competition. However, brain cell-nuclear ALD appeared not to vary as a function of physiological variation in serum ALD, suggesting that the receptor population was saturated under most normal circumstances. Unexpectedly, the highest cell-nuclear concentrations of endogenous ALD were found in the hypothalamus, rather than hippocampus. This finding suggests that the predominantly hippocampal localization of ALD observed in previous in vivo autoradiographic studies may have provided an inaccurate profile of the loci of ALD action in brain by failing to control for competitive binding by other corticosteroids in the adrenal-intact preparation.