Effects of dietary sodium restriction and potassium intake on cholesterol side-chain cleavage cytochrome P-450 and adrenodoxin mRNA levels.

Abstract

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.