Transcriptional activation of adrenocortical steroidogenic genes by high potassium or low sodium intake.
We have previously shown that the long-term alterations in the intake of sodium and potassium which stimulated aldosterone production in the rat adrenal significantly increased cytochrome P450scc (P450scc) and P45011 beta (P45011 beta) mRNA's and also the mRNA of their electron donor adrenodoxin. In the present study run-on analyses showed an accumulation of nascent RNA in isolated nuclei of zona glomerulosa cells in K(+)-supplemented and Na(+)-depleted rats for P450scc (5- and 6-fold), 3 beta-HSD (3.6- and 2.0-fold) and P45011 beta (6.0- and 6.1-fold), but not for P450c21 (1.4- and 1.1-fold). In contrast, that of adrenodoxin decrease (0.6-fold) in high K+ and remained near control (1.3-fold) in low Na+ intake. Moderate variations in the rate of transcription of P450scc, P450c21, P45011 beta and adrenodoxin genes were observed in the zona fasciculata-reticularis cells of the treated rats. Our results thus demonstrated that positive modulators of aldosterone such as long-term K+ supplementation and Na+ restriction provoked an increase in transcription of the genes encoding key regulatory steroidogenic enzymes of aldosterone biosynthesis in the zona glomerulosa. The rates of transcription of the genes encoding 3 beta-HSD and P450c21, two enzymes catalyzing intermediate steps in the aldosterone pathway, were moderately affected by such treatments. However, according to the known stimulation of adrenodoxin mRNA levels following these treatments, a decreased turnover of the adrenodoxin mRNA rather than initiation of transcription of its gene might be involved in the response to K+ ions, and partially so in the response to Na+ restriction. Finally, the effects of salt-modified intake were mainly restricted to the zona glomerulosa cells, which are solely responsible for aldosterone production.
Tremblay
A
A
Department of Biochemistry, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
LeHoux
J G
JG
D000302:Adrenal Cortex / Q000737:chemistry; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000450:Aldosterone / Q000097:blood; D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry; D003345:Corticosterone / Q000097:blood; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D017419:Potassium, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D012313:RNA / Q000032:analysis; D051381:Rats; D012083:Renin / Q000097:blood; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D014158:Transcription, Genetic
D000305:Adrenal Cortex Hormones; D017419:Potassium, Dietary; D012982:Sodium, Dietary; D000450:Aldosterone; D012313:RNA; D012083:Renin; D003345:Corticosterone