Biphasic autoregulation of mineralocorticoid receptor mRNA in the medial septal nucleus by aldosterone.

The time-dependent action of aldosterone was analyzed on the regulation of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNAs in the brain. Bilaterally adrenalectomized rats were injected subcutaneously with a single low dose of aldosterone (0.01 mg/kg, s.c.). By means of in situ hybridization MR and GR mRNA levels were studied in autoradiograms 2, 4, 8 and 24 h after the hormone injection in brain regions related to stress responses, i.e. subregions of the dorsal hippocampus (CA1 to CA4 and dentate gyrus), the hypothalamic paraventricular nucleus, and the septum. The findings show a biphasic regulation of MR mRNA levels in the medial septal nucleus with substantial increases after 4 h (79% increase) followed by substantial decreases in MR mRNA levels after 24 h (71% decrease), whereas no changes in MR mRNA levels were observed in the lateral septal nucleus. A negative autoregulation of hippocampal MR mRNA levels was observed only in the CA2 subregion (38% decrease) at the 8-hour time interval. Over the same time interval a negative cross-regulation of GR mRNA by aldosterone was observed in all hippocampal subfields (32-57% decrease) except in CA2. No changes in GR mRNA levels were found in the hypothalamic paraventricular nucleus. The time-dependent action of corticosterone (10 mg/kg, s.c.) was analyzed in the same animal model revealing no changes in MR mRNA levels in the medial and lateral septal nuclei. The present findings suggest that the medial septal nucleus shows a unique responsiveness to aldosterone in the adrenalectomized model in terms of biphasic changes in MR mRNA levels. Activated MR in the medial septal nucleus may therefore take part in the regulation of septo-hippocampal cholinergic pathways and thus of limbic circuits.