Development of adrenal zonation in fetal rats defined by expression of aldosterone synthase and 11beta-hydroxylase.
Development of adrenal zonation in fetal rats defined by expression of aldosterone synthase and 11beta-hydroxylase.
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DOI：
10.1210/en.139.10.4397
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发表时间：
1998
期刊：
影响因子：
4.8
通讯作者：
C. Wotus;B. Levay-Young;L. Rogers;C. Gomez-Sanchez;W. Engeland
中科院分区：
文献类型：
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作者：
C. Wotus;B. Levay-Young;L. Rogers;C. Gomez-Sanchez;W. Engeland
成年大鼠肾上腺皮质由三个同心的类固醇生成区组成，它们在形态和功能上是可区分的：肾小球、中间层和束状/网状层。区域特异性类固醇生成酶，细胞色素P450醛固酮合成酶（P450 aldo）和P450 11 β羟化酶（P45011 β）的表达，分别由肾小球和束状/网状肾上腺产生，可用于定义这两个区域的肾上腺皮质细胞表型。在这项研究中，免疫组织化学和原位杂交，以确定P450 aldo和P45011 β的表达的个体发育监测模式的大鼠肾上腺皮质。放射免疫分析法测定肾上腺醛固酮和皮质酮的含量，这两种酶途径的产物。在妊娠第16天（E16），两种酶的双重免疫荧光染色显示，P45011 β蛋白在分布于大部分肾上腺的细胞中表达，与表达P450 aldo蛋白的单独但较小的细胞群混合。而P45011 β蛋白的表达保持了类似的模式，从E16到成年（忽略SA-1阳性，假定髓细胞的分布），P450 aldo蛋白改变了其分布模式，E19，成为本地化在一个不连续的环的细胞相邻的胶囊。出生后第1天，P450 aldo蛋白的分布是类似的成年腺体中观察到的，P450 aldo阳性细胞形成一个连续的区域下面的胶囊。原位杂交显示P45011 β mRNA在E19和E19后均表达，而P45011 β mRNA在E19前未检测到。然而，肾上腺醛固酮和皮质酮，通过放射免疫测定，检测到E16，支持所有年龄段的研究的两种表型的功能能力。这些数据表明，发展的肾上腺皮质球状体发生在两个不同的阶段;球状体表型的初始表达在E17之前的内皮层的分散细胞，其次是E17和E19之间的分布到外皮层的变化。据推测，这种分布的变化发生通过细胞分化，而不是细胞迁移，这些事件的一个可能的调节因子是胎儿肾素-血管紧张素系统。
The adult rat adrenal cortex is comprised of three concentric steroidogenic zones that are morphologically and functionally distinguishable: the zona glomerulosa, zona intermedia, and the zona fasciculata/reticularis. Expression of the zone-specific steroidogenic enzymes, cytochrome P450 aldosterone synthase (P450aldo), and P450 11beta hydroxylase (P45011beta), produced by the zona glomerulosa and zona fasciculata/reticularis, respectively, can be used to define the adrenal cortical cell phenotype of these two zones. In this study, immunohistochemistry and in situ hybridization were used to determine the ontogeny of expression of P450aldo and P45011beta to monitor the pattern of development of the rat adrenal cortex. RIA was used to measure adrenal content of aldosterone and corticosterone, the resulting products of the two enzymatic pathways. Double immunofluorescent staining for both enzymes at gestational day 16 (E16) showed P45011beta protein expressed in cells distributed throughout most of the adrenal intermixed with a separate, but smaller, population of cells expressing P450aldo protein. Whereas expression of P45011beta protein retained a similar pattern of distribution from E16 to adulthood (ignoring distribution of SA-1 positive, presumptive medullary cells), P450aldo protein changed its pattern of distribution by E19, becoming localized in a discontinuous ring of cells adjacent to the capsule. By postnatal day 1, P450aldo protein distribution was similar to that observed in adult glands; P450aldo-positive cells formed a continuous zone underlying the capsule. In situ hybridization showed that the pattern of P45011beta messenger RNA expression paralleled protein expression at all times, whereas P450aldo messenger RNA paralleled protein at E19 and after, but was undetectable before E19. However, adrenal aldosterone and corticosterone, as measured by RIA, were detected by E16, supporting the functional capacity of both phenotypes for all ages studied. These data suggest that the development of the adrenal zona glomerulosa occurs in two distinct phases; initial expression of the glomerulosa phenotype in scattered cells of the inner cortex before E17, followed by a change in distribution to the outer cortex between E17 and E19. It is hypothesized that this change in distribution occurs via cell differentiation, rather than cell migration, and that a possible regulator of these events is the fetal renin-angiotensin system.