Regulation of aldosterone synthase gene expression in the rat adrenal gland and central nervous system by sodium and angiotensin II

Endocrinology. 2003 Aug;144(8):3321-8. doi: 10.1210/en.2003-0109.

Abstract

We have developed a highly sensitive QRT-PCR method for the measurement of CYP11B1 (11beta-hydroxylase) and CYP11B2 (aldosterone synthase) mRNAs to study their expression in the rat brain in response to dietary sodium manipulation and angiotensin (Ang)II infusion. Male Wistar Kyoto rats (n = 6) were fed normal, high, or low sodium diets for 12 d or were administered AngII or vehicle for 7 d. CYP11B2 and CYP11B1 expression was measured in RNA from adrenal gland and discrete brain regions using real-time QRT-PCR. Sodium restriction increased adrenal CYP11B2 expression 57-fold from 1.0 x 10(5) +/- 0.6 x 10(5) to 57 x 10(5) +/- 22 x 10(5) copies/ microg RNA (mean +/- SEM; P < 0.05);in the hippocampus, 14-fold from 5.4 x 10(2) +/- 0.8 x 10(2) to 74 x 10(2) +/- 31 x 10(2) copies/ microg RNA (P < 0.05); and in the cerebellum, 5-fold from 1.9 x 10(3) +/- 0.7 x 10(3) to 9.9 x 10(3) +/- 3.0 x 10(3) copies/ microg RNA (P < 0.01). CYP11B2 gene expression in the brainstem and hypothalamus was not affected. High-sodium diet reduced adrenal CYP11B2 expression to 0.19 x 10(5) +/- 0.1 x 10(5) copies/ microg RNA (P < 0.05) but did not affect central nervous system (CNS) expression significantly. AngII significantly increased adrenal CYP11B2 expression but did not affect CNS expression. Brain CYP11B1 mRNA levels were 10- to 1000-fold higher than CYP11B2 but were unaffected by dietary sodium or AngII. To summarize, we have identified a local CYP11B2 response to sodium depletion in the hippocampus and cerebellum. This is the first such regulation of CYP11B2 transcription to be identified in the CNS.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / blood
  • Adrenal Glands / enzymology*
  • Aldosterone / blood
  • Angiotensin II / administration & dosage
  • Angiotensin II / pharmacology*
  • Animals
  • Brain / enzymology*
  • Cerebellum / enzymology
  • Cytochrome P-450 CYP11B2 / genetics*
  • Diet, Sodium-Restricted
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Hippocampus / enzymology
  • Kinetics
  • Male
  • RNA, Messenger / analysis
  • Rats
  • Rats, Inbred WKY
  • Renin / blood
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sodium, Dietary / administration & dosage
  • Sodium, Dietary / pharmacology*
  • Steroid 11-beta-Hydroxylase / genetics

Substances

  • Adrenal Cortex Hormones
  • RNA, Messenger
  • Sodium, Dietary
  • Angiotensin II
  • Aldosterone
  • Cytochrome P-450 CYP11B2
  • Steroid 11-beta-Hydroxylase
  • Renin