Transcriptional activation of adrenocortical steroidogenic genes by high potassium or low sodium intake

Abstract

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 P450 scc (P450 scc) and P450 l11β (P450 11β) 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 P450 c (5- and 6-fold), 3β-HSD (3.6- and 2.0-fold) and P450 11β (6.0- and 6.1-fold), but not for P450 c21 (1.4- and 1.1-fold). In contrast, that of adrenodoxin decreased (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 P450 scc, P450 c21, P450 11β 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 3β-HSD and P450 c21, 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.