Effects of dietary sodium restriction and potassium intake on cholesterol side-chain cleavage cytochrome P-450 and adrenodoxin mRNA levels.
We studied the effect of dietary sodium restriction (3 weeks) and high potassium intake (7 days) on transcriptional regulation of cytochrome P-450 cholesterol side chain cleavage (P-450 scc) and adrenodoxin (Adx) in rat adrenal glands. Northern blotting analysis demonstrated that both treatments markedly increased P-450scc and Adx mRNA levels in the zona glomerulosa (Z-G) and the zona fasciculata-reticularis (Z-F-R) compared with controls. The Z-G appears to be more sensitive to variations in electrolytes than does the Z-F-R. The low sodium diet provoked a 2.9-fold increase in P-450scc mRNA level in the Z-G compared to 2.1-fold in the Z-F-R, whereas Adx mRNA levels were enhanced 2.2- and 1.7-fold respectively in these two zones. Restriction of sodium intake provoked significant increases in plasma ACTH, aldosterone and corticosteroids compared with controls. In the Z-G of KCl-loaded rats, we found a 1.6-fold increase in P-450scc and a 2.1-fold increase in Adx mRNA levels, and in the Z-F-R there was a 1.7- and 1.8-fold enhancement. There were no changes in beta-actin mRNA levels upon dietary treatments. These results thus indicate that both sodium depletion and high potassium intake in rats could act at the transcriptional level of P-450scc and Adx, two components of a rate-limiting step in steroidogenesis leading to aldosterone production. In addition, the elevation in plasma ACTH level in response to Na+ restriction suggests a possible involvement of ACTH in the response of the adrenal glands to sodium depletion.
Tremblay
A
A
Department of Biochemistry, Faculty of Medicine, University of Sherbrooke, Québec, Canada.
Lehoux
J G
JG
D000199:Actins / Q000235:genetics; D000311:Adrenal Glands / Q000187:drug effects / Q000201:enzymology*; D000325:Adrenodoxin / Q000235:genetics*; D000818:Animals; D015152:Blotting, Northern; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics*; D015342:DNA Probes; D004039:Diet, Sodium-Restricted; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D011188:Potassium / Q000494:pharmacology; D011191:Potassium Deficiency / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D012016:Reference Values; D014158:Transcription, Genetic
D000199:Actins; D015342:DNA Probes; D012333:RNA, Messenger; D000325:Adrenodoxin; D002786:Cholesterol Side-Chain Cleavage Enzyme; D011188:Potassium