Modulation of aldosterone synthase messenger ribonucleic acid levels by dietary sodium and potassium and by adrenocorticotropin.
Recent evidence suggests that an aldosterone synthase (AS) separate from the 11 beta-hydroxylase (11 beta-OHase) mediates the final step(s) in aldosterone synthesis in the rat. We have compared changes in AS and 11 beta-OHase mRNA levels with experimental maneuvers known to stimulate or suppress aldosterone secretion. In Exp 1, male rats were fed regular rat chow (group 1), a low sodium, high potassium diet (group 2), or a high sodium, low potassium diet (group 3). Northern analysis of adrenal capsular (zona glomerulosa) and decapsulated adrenal core (fasciculata-reticularis) tissues was performed with specific oligonucleotide probes for AS and 11 beta-OHase mRNAs, normalized with a cDNA probe for 18S ribosomal RNA (rRNA). There was a marked increase in capsular AS mRNA in group 2 rats compared to levels in group 1 (P < 0.0001) and group 3 (P < 0.0001) rats. Capsular As mRNA decreased (P < 0.05) in group 3 compared to that in group 1 rats. Adrenal core AS mRNA levels were quite low with all three diets. In contrast, capsular and core 11 beta-OHase mRNA levels did not change significantly with diet. In Exp 2, two groups served as controls (groups 1 and 3), and two groups received sc injections of repository ACTH (groups 2 and 4). Control and ACTH-treated rats were killed 3 h (groups 1 and 2) or 24 h (groups 3 and 4) after initial ACTH administration. Capsular and core AS and 11 beta-OHase mRNA levels were evaluated with and without normalization with 18S rRNA, cyclophilin, and glyceraldehyde phosphate dehydrogenase housekeeping probes. Capsular AS mRNA increased at 3 h (P < 0.05), but decreased at 24 h (P < 0.01). Nonnormalized adrenal capsular and core 11 beta-OHase mRNA levels were unchanged at 3 h, but increased significantly at 24 h (P < 0.05) in capsular tissue of ACTH-treated rats. However, in ACTH-treated rats, 18S rRNA and cyclophilin mRNA levels increased at 24 h in both capsular and core tissue (P < 0.01), and glyceraldehyde phosphate dehydrogenase mRNA levels increased in capsular tissue (P < 0.00001), resulting in a lack of change in normalized 11 beta-OHase mRNA. Changes in cholesterol side-chain cleavage were similar to those in 11 beta-OHase mRNA. These data provide further evidence that a separate AS plays a significant role in modulating aldosterone secretion in rodents.
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-1060.
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D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D019405:Cytochrome P-450 CYP11B2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004032:Diet; D008297:Male; D011188:Potassium / Q000008:administration & dosage* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000008:administration & dosage* / Q000494:pharmacology; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics; D013250:Steroid Hydroxylases / Q000235:genetics*
D012333:RNA, Messenger; D000324:Adrenocorticotropic Hormone; D003577:Cytochrome P-450 Enzyme System; D012964:Sodium; D013250:Steroid Hydroxylases; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase; D011188:Potassium