Regulation of aldosterone synthase gene expression in the rat adrenal gland and central nervous system by sodium and angiotensin II.
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.
Ye
Ping
P
Medical Research Council Blood Pressure Group, Western Infirmary, Glasgow, Scotland G11 6NT, United Kingdom.
Kenyon
Christopher J
CJ
MacKenzie
Scott M
SM
Seckl
Jonathan R
JR
Fraser
Robert
R
Connell
John M C
JM
Davies
Eleanor
E
D000305:Adrenal Cortex Hormones / Q000097:blood; D000311:Adrenal Glands / Q000201:enzymology*; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002531:Cerebellum / Q000201:enzymology; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D004039:Diet, Sodium-Restricted; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006624:Hippocampus / Q000201:enzymology; D007700:Kinetics; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011921:Rats, Inbred WKY; D012083:Renin / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics
D000305:Adrenal Cortex Hormones; D012333:RNA, Messenger; D012982:Sodium, Dietary; D000804:Angiotensin II; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase; D012083:Renin