Regulation of angiotensinogen gene expression in the rat forebrain by adrenal steroids and relation to salt appetite.
The renin-angiotensin system (RAS) is present in the brain where it participates in regulation of fluid-electrolyte homeostasis and possibly plays a role in arousal of salt appetite. In the present studies using quantitative in situ hybridization histochemistry we examined the level of the angiotensinogen (ANG) mRNA in the forebrain areas associated with fluid-electrolyte balance in adrenalectomized (ADX) rats and ADX rats supplemented either with selective glucocorticoid type II receptor agonist RU 28362 or with the selective type I receptor agonist, aldosterone (ALDO). RU 28362 and ALDO were administered for 7 days via Alzet 2001 osmotic minipumps at the rates of 10 micrograms/microliters/h and 1 microgram/microliter/h, respectively. Following adrenalectomy, rats were maintained on a standard rat chow, water and 3% NaCl ad lib. In situ hybridization was performed either with a synthetic [33P]- or [32P]-3' end-labeled oligonucleotide probe and the level of ANG mRNA was detected by grain counting over a single cell or by quantitative film autoradiography, respectively. Seven days post ADX the ANG mRNA level in all studied forebrain areas -septum-diagonal band of Broca (SEPT/DBB), the areas immediately adjacent to the organum vasculosum of the lamina terminalis (OVLT), the median preoptic nucleus (MnPO), and the medial preoptic area (mPOA)-of ADX rats decreased by 50-60%. ALDO treatment, which did prevent ADX-induced saline ingestion, did not prevent this decrease. However, supplementation with RU 28362 maintained normal levels of ANG mRNA in all the above regions of the brain. Thus the expression of the ANG gene in the studied areas of rat forebrain is predominantly under the control of the adrenal glucocorticoids via the type II receptor and not regulated by an ALDO dose that stabilizes natriuresis from the kidney.
Riftina
F
F
Laboratory of Neuroendocrinology, Rockefeller University, New York, NY 10021, USA.
Angulo
J
J
Pompei
P
P
McEwen
B
B
D000302:Adrenal Cortex / Q000502:physiology*; D000315:Adrenalectomy; D000450:Aldosterone / Q000494:pharmacology*; D000704:Analysis of Variance; D000732:Androstanols / Q000494:pharmacology*; D000808:Angiotensinogen / Q000096:biosynthesis*; D000818:Animals; D001066:Appetite; D001483:Base Sequence; D005786:Gene Expression Regulation / Q000187:drug effects; D017403:In Situ Hybridization; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D009928:Organ Specificity; D010761:Phosphorus Radioisotopes; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012965:Sodium Chloride; D014882:Water-Electrolyte Balance
D000732:Androstanols; D015345:Oligonucleotide Probes; D010761:Phosphorus Radioisotopes; D000808:Angiotensinogen; D012965:Sodium Chloride; D000450:Aldosterone; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one