The a7 subunit is a component of nicotinic acetylcholine receptors expressed in bovine chromaffin cells. The peculiar localization of these receptors at adrenomedullary areas adjacent to the adrenal cortex suggests that factors, probably glucocorticoids, arising from the cortex might diffuse and regulate a7 receptor expression. In reporter gene transfection experiments, dexamethasone increased a7 promoter activity by up to fivefold in a concentration-and time-dependent manner despite the absence of consensus glucocorticoid receptor elements at the a7 promoter. Transcriptional activation induced by glucocorticoids was abolished through simultaneous mutation of at least two of the three sites for the immediate early transcription factor Egr-1, present in the proximal promoter region of the a7 subunit gene. Therefore, glucocorticoids activate the a7 subunit gene through Egr-1 in an indirect way.