Divergent differentiation of rat adrenocortical cells is associated with an interruption of angiotensin II-mediated signal transduction

Abstract

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-trisphosphate. In contrast, the two cell types exhibited very different Ang II-mediated changes in free intracellular calcium ([Ca 2+] i). Ang II (10 nM), induced [Ca 2+] i increases of > 50 nM in 90% of individual GLOM cells ( 53 58 ), but in only 28% of FASC cells ( 11 39 ). These [Ca 2+] 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 [Ca 2+] 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 [Ca 2+] i increases in both populations. Importantly, a calcium ionophore induced elevation of [Ca 2+] 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).