Modulation of aldosterone synthase messenger ribonucleic acid levels by dietary sodium and potassium and by adrenocorticotropin.
Modulation of aldosterone synthase messenger ribonucleic acid levels by dietary sodium and potassium and by adrenocorticotropin.
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膳食钠和钾以及促肾上腺皮质激素对醛固酮合酶信使核糖核酸水平的调节。
DOI：
10.1210/endo.132.6.8389287
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发表时间：
1993
期刊：
影响因子：
4.8
通讯作者：
B. Carr
中科院分区：
文献类型：
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作者：
O. Holland;B. Carr
最近的证据表明，与 11 β-羟化酶 (11 β-OHase) 分开的醛固酮合酶 (AS) 介导大鼠醛固酮合成的最后步骤。我们将 AS 和 11 β-OHase mRNA 水平的变化与已知刺激或抑制醛固酮分泌的实验操作进行了比较。在实验1中，给雄性大鼠喂食常规大鼠饲料（第1组）、低钠、高钾饮食（第2组）或高钠、低钾饮食（第3组）。使用 AS 和 11 β-OHase mRNA 的特异性寡核苷酸探针对肾上腺囊（球状带）和脱囊肾上腺核心（束状网状肌）组织进行 Northern 分析，并使用 18S 核糖体 RNA (rRNA) 的 cDNA 探针进行标准化。与第 1 组 (P < 0.0001) 和第 3 组 (P < 0.0001) 大鼠的水平相比，第 2 组大鼠的囊膜 AS mRNA 显着增加。与第 1 组大鼠相比，第 3 组大鼠的荚膜 As mRNA 降低（P < 0.05）。所有三种饮食的肾上腺核心 AS mRNA 水平都相当低。相比之下，荚膜和核心 11 β-OHase mRNA 水平并没有随饮食发生显着变化。在实验 2 中，两组作为对照（组 1 和组 3），两组接受皮下注射储存 ACTH（组 2 和组 4）。首次给予 ACTH 后 3 小时（第 1 组和第 2 组）或 24 小时（第 3 组和第 4 组）处死对照和 ACTH 治疗的大鼠。在使用或不使用 18S rRNA、亲环蛋白和磷酸甘油醛脱氢酶管家探针进行标准化的情况下，评估荚膜和核心 AS 以及 11 β-OHase mRNA 水平。荚膜AS mRNA在3小时时增加（P < 0.05），但在24小时时减少（P < 0.01）。在 ACTH 治疗的大鼠的囊组织中，非标准化肾上腺囊和核心 11β-OHase mRNA 水平在 3 小时时没有变化，但在 24 小时时显着增加（P < 0.05）。然而，在ACTH治疗的大鼠中，24小时后囊膜和核心组织中18S rRNA和亲环蛋白mRNA水平均增加（P < 0.01），囊组织中磷酸甘油醛脱氢酶mRNA水平增加（P < 0.00001），导致标准化11β-OHase mRNA没有变化。胆固醇侧链裂解的变化与 11β-OHase mRNA 的变化相似。这些数据进一步证明，单独的 AS 在调节啮齿动物醛固酮分泌方面发挥着重要作用。
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.
Shibata,H.、Ogishima,T.、Mitani,F.、Suzuki,H.、Murakami,M.、Saruta,T. 和 Ishimura,Y.：“血管紧张素对大鼠肾上腺醛固酮合酶细胞色素 P-450 的调节
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