Expression of Mineralocorticoid and Glucocorticoid Receptors In Pre-autonomic Neurons of the Rat Paraventricular Nucleus
AJP Regulatory Integrative and Comparative Physiology
Published online on December 31, 2013
Abstract
Activation of mineralocorticoid receptors (MR) of the hypothalamic paraventricular nucleus (PVN) increases sympathetic excitation. To determine whether MR and glucocorticoid receptors (GR) are expressed in pre-autonomic neurons of the PVN and how they relate to endogenous aldosterone levels in healthy normotensive rats, retrograde tracer was injected into the intermediolateral cell column at T4 to identify pre-autonomic neurons in the PVN. Expression of MR, GR, 11-β hydroxysteroid dehydrogenase1 & 2 (11βHSD1&2), and hexose-6-phosphate dehydrogenase (H6PD) required for 11βHSD1 reductase activity by immunohistochemistry. RT-PCR and western blot analysis was used to determine MR gene and protein expression. Most pre-autonomic neurons were in the caudal mediocellular region of PVN and most expressed MR; none expressed GR. 11βHSD1, but not 11βHSD2 or H6PD immunoreactivity, was detected in the PVN. In rats receiving chronic low or high sodium intakes, the low sodium diet was associated with significantly higher plasma aldosterone, MR mRNA and protein expression, and c-fos immunoreactivity within pre-autonomic neurons. Plasma corticosterone and sodium and expression of tonicity-responsive enhancer binding protein in the PVN did not differ between groups, suggesting osmotic adaptation to the altered sodium intake. These results suggest that MR within pre-autonomic neurons in the PVN directly participate in the regulation of sympathetic nervous system drive, aldosterone may be a relevant ligand for MR in pre-autonomic neurons of the PVN under physiological conditions due to the dehydrogenase activity of 11βHSD1 in the absence of H6PD that regenerates NADP+ from NADPH and may increase MR gene expression under physiological conditions.