Angiotensinogen and Natriuretic Peptide mRNAs in Rat Brain: Localization and Differential Regulation by Adrenal Steroids in Hypothalamus

Abstract

Ryan, M. C., P.-J. Shen and A. L. Gundlach. Angiotensinogen and natriuretic peptide mRNAs in rat brain: localization and differential regulation by adrenal steroids in hypothalamus. Peptides 18(4) 495–504, 1997.—Adrenal steroids have been shown to modulate angiotensin II and natriuretic peptide systems—peptide synthesis and metabolism—in vitro. In the present study the effects of adrenal steroids on mRNA encoding the angiotensin II precursor, angiotensinogen (AOGEN), and the natriuretic peptides, atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) in the rat hypothalamus were investigated using quantitative in situ hybridization histochemistry of [ 35S]- and [ 33P]-labeled oligonucleotide probes. Adrenalectomy produced an apparent overall decrease in preproAOGEN (ppAOGEN) mRNA in presumed astrocytes in the anterior hypothalamus with significant decreases (ANOVA) measured in the medial preoptic area, the ventral region of the medial preoptic area, the paraventricular, suprachiasmatic, supraoptic, and periventricular nuclei. ppAOGEN mRNA levels were restored by both glucocorticoid (dexamethasone; 2 μg/ml in drinking water) and mineralocorticoid (aldosterone; 50 μg/kg, SC) replacement. Treatment of intact animals with dexamethasone (2 μg/ml in drinking water for 5 days) and aldosterone (100 μg/kg, SC, daily for 10 days) produced a significant increase in ppAOGEN mRNA in those hypothalamic regions affected by adrenalectomy. ppANP and ppCNP mRNA-positive neurons were successfully detected using [ 35S]- and [ 33P]-labeled probes, respectively, and were abundant in the anterior hypothalamus, particularly in the anteromedial preoptic nucleus of the medial preoptic area. In contrast to the effects on ppAOGEN mRNA, however, alterations in adrenal steroid levels did not significantly change ppANP or ppCNP mRNA levels in neurons of the anteromedial preoptic nucleus or in the arcuate nucleus. These results indicate that adrenal steroids modulate AOGEN gene transcription in vivo, consistent with previous reports of increased levels of ppAOGEN mRNA in a number of brain regions in response to acute dexamethasone treatment and reports of decreased AOGEN immunoreactivity in brain regions of adrenalectomized rats. In contrast, despite reports of modulation of hypothalamic ANP immunoreactivity following adrenalectomy and dexamethasone treatment, it would appear that adrenal steroids do not alter the transcription or stability of hypothalamic natriuretic peptides mRNA in vivo.