Roskelley C D, Baimbridge K G, Leung P C, Auersperg N
Department of Anatomy, University of British Columbia, Vancouver, Canada.
Mol Cell Endocrinol. 1992 Nov;89(1-2):79-89. doi: 10.1016/0303-7207(92)90213-p.
The zones of the adrenal cortex contain distinct populations of cells which share a common developmental origin and steroidogenic template. In the rat, zona glomerulosa cells respond to angiotensin II (Ang II) with increased steroidogenesis while zona fasciculata/reticularis cells do not. We have examined Ang II-mediated signal transduction in homogeneous cellular sub-populations derived from either the zona glomerulosa (GLOM) or the zona fasciculata (FASC). In both of these sub-populations Ang II treatment significantly increased the levels of 3H-labelled inositol phosphates as well as the total mass of inositol 1,4,5-triphosphate. In contrast, the two cell types exhibited very different Ang II-mediated changes in free intracellular calcium ([Ca2+]i). Ang II (10 nM), induced [Ca2+]i increases of > 50 nM in 90% of individual GLOM cells (53/58), but in only 28% of FASC cells (11/39). These [Ca2+]i responses occurred after a transient Ang II stimulation ( < 1 min), in the presence of verapamil and in the absence of extracellular calcium, indicating an intracellular release. In small groups of 10-30 cells, stimulation with 1, 10 and 100 nM Ang II induced [Ca2+]i increases of 78, 178 and 215 nM respectively in GLOM cultures compared to only 35, 64, and 65 nM in FASC cultures. Thapsigargin treatment, which releases intracellular calcium in an inositol phosphate independent manner, elicited [Ca2+]i increases in both populations. Importantly, a calcium ionophore induced elevation of [Ca2+]i increased steroidogenesis in both cell types. These results suggest that an interruption of the signaling cascade at the level of intracellular calcium release contributes to the lack of a steroidogenic response to Ang II by the FASC cells. Therefore, in the rat adrenal cortex, divergent differentiation of related cell types may involve alterations within signal transduction pathways distal to initial receptor-mediated events (i.e. inositol phosphate production) and proximal to downstream effector events (i.e. steroidogenesis).
肾上腺皮质的不同区域含有不同的细胞群体，它们具有共同的发育起源和类固醇生成模板。在大鼠中，球状带细胞对血管紧张素II（Ang II）产生反应，类固醇生成增加，而束状带/网状带细胞则无此反应。我们研究了源自球状带（GLOM）或束状带（FASC）的同质细胞亚群中Ang II介导的信号转导。在这两个亚群中，Ang II处理均显著增加了3H标记的肌醇磷酸水平以及肌醇1,4,5 - 三磷酸的总量。相比之下，两种细胞类型在细胞内游离钙（[Ca2+]i）方面表现出非常不同的Ang II介导的变化。Ang II（10 nM）可使90%的单个GLOM细胞（53/58）中的[Ca2+]i增加>50 nM，但仅使28%的FASC细胞（11/39）中的[Ca2+]i增加。这些[Ca2+]i反应在短暂的Ang II刺激（<1分钟）后出现，在维拉帕米存在且细胞外无钙的情况下发生，表明是细胞内钙释放。在10 - 30个细胞的小群体中，用1、10和100 nM的Ang II刺激分别使GLOM培养物中的[Ca2+]i增加78、178和215 nM，而FASC培养物中仅增加35、64和65 nM。毒胡萝卜素处理以不依赖肌醇磷酸的方式释放细胞内钙，在两个群体中均引起[Ca2+]i增加。重要的是，钙离子载体诱导的[Ca2+]i升高在两种细胞类型中均增加了类固醇生成。这些结果表明，细胞内钙释放水平的信号级联中断导致FASC细胞对Ang II缺乏类固醇生成反应。因此，在大鼠肾上腺皮质中，相关细胞类型的不同分化可能涉及初始受体介导事件（即肌醇磷酸产生）远端和下游效应事件（即类固醇生成）近端的信号转导途径内的改变。
