Transcriptional and physiological responses to chronic ACTH treatment by the mouse kidney.
Transcriptional and physiological responses to chronic ACTH treatment by the mouse kidney.
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DOI：
10.1152/physiolgenomics.00088.2009
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发表时间：
2010-02-04
影响因子：
4.6
通讯作者：
Bailey MA
中科院分区：
文献类型：
--
作者：
Dunbar DR;Khaled H;Evans LC;Al-Dujaili EA;Mullins LJ;Mullins JJ;Kenyon CJ;Bailey MA
我们研究了长期输注 ACTH 对小鼠尿类固醇和电解质排泄以及肾脏基因表达的影响。 ACTH 导致皮质类固醇排泄持续增加；醛固酮排泄仅短暂升高。脱氧皮质酮（一种弱盐皮质激素）的排泄增加至具有生理意义的水平。然而，我们在 ACTH 治疗的小鼠中既没有观察到抗尿钠排尿现象，也没有观察到排钾现象，血浆肾素活性也没有受到抑制。我们发现盐皮质激素靶基因的表达没有变化。慢性 ACTH 治疗小鼠的水周转率增加，血细胞比容和高渗性也增加：容量收缩与高水平的糖皮质激素一致。接受 ACTH 治疗的小鼠表现出糖皮质激素过量的其他迹象，例如体重增加增加和胸腺退化。我们发现了 ACTH 引起的新变化：1) 与钙尿和磷酸尿相关的维生素 D（Cyp27b1、Cyp24a1、Gc）和钙（Sgk、Calb1、Trpv5）代谢相关的基因； 2) 预计会使肾脏对糖皮质激素作用脱敏的基因（Nr3c1、Hsd11b1、Fkbp5）； 3）编码与外源代谢和氧化应激相关的酶系统转运蛋白的基因。尽管有证据表明 ACTH 诱发的高血压是糖皮质激素和盐皮质激素之间生理相互作用的结果，但本研究表明电解质和体液稳态以及肾功能的主要变化可归因于糖皮质激素。受 ACTH 影响的钙和有机阴离子代谢途径可以解释与糖皮质激素过量相关的一些已知不良反应。
We investigated the effects on urinary steroid and electrolyte excretion and renal gene expression of chronic infusions of ACTH in the mouse. ACTH caused a sustained increase in corticosteroid excretion; aldosterone excretion was only transiently elevated. There was an increase in the excretion of deoxycorticosterone, a weak mineralocorticoid, to levels of physiological significance. Nevertheless, we observed neither antinatriuresis nor kaliuresis in ACTH-treated mice, and plasma renin activity was not suppressed. We identified no changes in expression of mineralocorticoid target genes. Water turnover was increased in chronic ACTH-treated mice, as were hematocrit and hypertonicity: volume contraction is consistent with high levels of glucocorticoid. ACTH-treated mice exhibited other signs of glucocorticoid excess, such as enhanced weight gain and involution of the thymus. We identified novel ACTH-induced changes in 1) genes involved in vitamin D (Cyp27b1, Cyp24a1, Gc) and calcium (Sgk, Calb1, Trpv5) metabolism associated with calciuria and phosphaturia; 2) genes that would be predicted to desensitize the kidney to glucocorticoid action (Nr3c1, Hsd11b1, Fkbp5); and 3) genes encoding transporters of enzyme systems associated with xenobiotic metabolism and oxidative stress. Although there is evidence that ACTH-induced hypertension is a function of physiological cross talk between glucocorticoids and mineralocorticoids, the present study suggests that the major changes in electrolyte and fluid homeostasis and renal function are attributable to glucocorticoids. The calcium and organic anion metabolism pathways that are affected by ACTH may explain some of the known adverse effects associated with glucocorticoid excess.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
19.6
作者：
Bailey, M. A.;Cantone, A.;Malnic, G.
通讯作者：
Malnic, G.
DOI：
10.1016/j.bbalip.2006.01.004
发表时间：
2006-02-01
影响因子：
4.8
作者：
Masuda, S;Strugnell, SA;Jones, G
通讯作者：
Jones, G
DOI：
10.1530/acta.0.1220599
发表时间：
1990-05-01
期刊：
ACTA ENDOCRINOLOGICA
影响因子：
--
作者：
KENYON, CJ;BROWN, WB;DAVIES, DL
通讯作者：
DAVIES, DL
影响因子：
13.6
作者：
Gaeggeler, HP;Gonzalez-Rodriguez, E;Rossier, BC
通讯作者：
Rossier, BC