Immunohistochemical analysis of AT(1) receptor versus P450c17 and 3 beta HSD expression in ovine adrenals.
Immunohistochemical analysis of AT(1) receptor versus P450c17 and 3 beta HSD expression in ovine adrenals.
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DOI：
10.1080/07435809609043717
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发表时间：
1996-01-01
影响因子：
2.1
通讯作者：
Conley, AJ
中科院分区：
文献类型：
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作者：
Bird, IM;Zheng, J;Conley, AJ
以往在体外对绵羊肾上腺皮质细胞的研究表明，血管紧张素II(AII)受体表达在束状带(ZF)细胞上，并在功能上与磷酸肌醇酶C偶联并增加[Ca~(2+)](I)，但所有AII受体的刺激并不会导致皮质醇生物合成的急剧变化。然而，AII可以长期调节P450c17和3βHSD在体外培养的绵羊肾上腺皮质细胞中的差异表达。我们用血管紧张素II 1型受体(AT1-R)以及P450c17和3βHSD的特异性抗血清对绵羊肾上腺切片进行染色，以进一步验证这样的假设，即ATI-R表达的变化是体内P450c17和3βHSD区带表达变化的基础。正如预期的那样，AT1-R在最外层的细胞(肾小球带，ZG)表达最高，P450c17阴性，3βHSD弱阳性。相邻细胞层(ZF)AT1-R染色较弱，而P450c17和3βHSD染色较强。这些发现与我们之前报道的体外表达数据一致，表明从ZG表型向ZF表型的转变，即P450c17和3βHSD表达的增加，可能需要AT1-R的表达减少，但在绵羊ZF中AT1-R表达的降低仍然允许对P450c17：3βHSD比率的差异控制。因此，即使在这些细胞中没有单独对AII的急性皮质醇反应，所有的II刺激可以对抗ZF对ACTH等激动剂的皮质醇生物合成中C19类固醇的产生。
Previous studies in ovine adrenocortical cells in vitro have shown angiotensin II (AII) receptors are expressed on the zona fasciculata (ZF) cells and are functionally coupled to phosphoinositidase C and increased [Ca2+](i), but AII stimulation does not cause an acute change in cortisol biosynthesis. AII can, however, chronically regulate differential expression of P450c17 and 3 beta HSD in ovine adrenocortical cells in vitro. We have stained ovine adrenal sections with specific antisera to the angiotensin II Type-1 receptor (AT1-R), as well as P450c17 and 3 beta HSD in order to further test the hypothesis that changes in ATI-R expression underlie changes in zonal expression of P450c17 and 3 beta HSD in vivo. AT1-R expression was found to be highest in the outermost layer of cells (zona glomerulosa, ZG) which stained negatively for P450c17 and only faintly positive for 3 beta HSD, as expected. The adjacent layer of cells (ZF) stained much less strongly for AT1-R but stronger for P450c17 and 3 beta HSD. These findings are consistent with our previously reported in vitro expression data, and suggest that the transition from ZG to ZF phenotype, i.e. increased P450c17 and 3 beta HSD expression, may require reduced expression of AT1-R, but maintenance of reduced levels of AT1-R expression in the ovine ZF still allows for differential control of the P450c17: 3 beta HSD ratio. Thus, even though there is no acute cortisol response to AII alone in these cells, AII stimulation can oppose C19 steroid production in the face of cortisol biosynthesis by the ZF in response to agonists such as ACTH.