Role of adrenal renin in the regulation of adrenal steroidogenesis by corticotropin.
Role of adrenal renin in the regulation of adrenal steroidogenesis by corticotropin.
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肾上腺肾素在促肾上腺皮质激素调节肾上腺类固醇生成中的作用。
DOI：
10.1073/pnas.91.1.148
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发表时间：
1994
影响因子：
11.1
通讯作者：
Mellon,SH
中科院分区：
文献类型：
--
作者：
Sander,M;Ganten,D;Mellon,SH
肾上腺产生盐皮质激素的主要调节因子是肾肾素作用产生的血管紧张素II。啮齿动物肾上腺也合成肾素和血管紧张素原的发现表明，盐皮质激素的合成存在自分泌调节。转基因大鼠[TGR(MREN2)27]主要在肾上腺表达REN-2d基因。尽管肾脏和血浆肾素受到抑制，但这些动物在5到15周大的时候会出现暴发性高血压。在高血压的发展过程中，皮质类固醇浓度显著升高。我们通过分析三种类固醇生成酶的mRNAs的表达来评估TGR(MREN2)27大鼠的类固醇生成：P450scc，类固醇生成的限速步骤；P450c11β，在束状带/网状带中将脱氧皮质酮转化为皮质酮；以及P450c11AS，在肾小球中将脱氧皮质酮转化为醛固酮。P450c11AS基因在TGR(MREN_2)27大鼠肾上腺中有高表达，但P450c11β和P450scc基因均不表达。用P450c11β和P450c11AS的特异性探针进行原位杂交，前者仅定位于束状带，后者定位于球状带。在TGR(MREN_2)27只大鼠中，肾上腺的大小和表达P450c11AS的肾小球细胞数约为正常SD大鼠的两倍。两种动物对促肾上腺皮质激素的反应相似；促肾上腺皮质激素对P450scc和P45011βmRNAs的表达没有影响，使P450c11as的mRNA无法检测到，同时改变了肾上腺皮质的形态，导致缺乏肾小球带样细胞。因此，局部肾素-血管紧张素系统对P450c11AS的基础表达有重要影响，但对促肾上腺皮质激素调节的P450scc、P450c11β和P450c11AS的mRNAs的表达影响不大。
The major regulator of mineralocorticoid production in the adrenal is angiotensin II produced by the action of renal renin. The discovery that the rodent adrenal also synthesizes renin and angiotensinogen suggests there is autocrine regulation of mineralocorticoid synthesis. The transgenic rat [TGR(mREN2)27] expresses the Ren-2d gene predominantly in the adrenal. Despite suppressed kidney and plasma renin, these animals develop fulminant hypertension between 5 and 15 weeks of age. Corticosteroid concentrations are significantly elevated during hypertension development. We assessed steroidogenesis in TGR(mREN2)27 rats by analyzing the expression of the mRNAs for three steroidogenic enzymes: P450scc, the rate-limiting step of steroidogenesis; P450c11 beta, which converts deoxycorticosterone to corticosterone in the zona fasciculata/reticularis; and P450c11AS, which converts deoxycorticosterone to aldosterone in the zona glomerulosa. P450c11AS mRNA, but neither P450c11 beta nor P450scc mRNA, was overexpressed in the adrenal gland of TGR(mREN2)27 rats. In situ hybridization with specific probes for P450c11 beta and P450c11AS mRNA localized the former exclusively to the zona fasciculata and the latter to the zona glomerulosa. In TGR(mREN2)27 rats, the size of the adrenal and number of P450c11AS-expressing zona glomerulosa cells were about twice those of a normal Sprague-Dawley rat. Both animals respond to corticotropin similarly; corticotropin had no effect on the expression of P450scc and P45011 beta mRNAs, rendered P450c11AS mRNA undetectable, and simultaneously altered the morphology of the adrenal cortex, resulting in a lack of zona glomerulosa-like cells. Thus, the local renin-angiotensin system has a major effect on the basal expression of P450c11AS mRNA, but little effect on the corticotropin-regulated expression of P450scc, P450c11 beta, and P450c11AS mRNAs.
肾外组织中的异肾素血管紧张素系统
DOI：
10.1111/j.1440-1681.1976.tb00596.x
发表时间：
1976
影响因子：
2.9
作者：
Detlev Ganten;J. S. Hutchinson;P. Schelling;U. Ganten;H. Fischer
通讯作者：
H. Fischer
啮齿动物组织中肾上腺素和 P450scc mRNA 的表达和调节。
影响因子：
3.1
作者：
Mellon,SH;Kushner,JA;Vaisse,C
通讯作者：
Vaisse,C