Significance Humans are constantly confronted with multiple stressors, to which the bodily response and adaptation are essential. The adrenal gland plays a major role in the response to physiological challenges. Maintenance of the adrenal is partly accomplished by proliferation and differentiation of adult progenitors and stem cells in the cortex and medulla. In this study, we have isolated and characterized a subpopulation of adrenocortical progenitors, which are interconnected with adrenomedullary stress-dependent progenitors. Under stress, the adrenocortical progenitors are also activated and they mobilize, giving rise to steroidogenic cells. Our findings demonstrate the coordinated action of stress-inducible stem cells to ensure tissue remodeling and cellular and functional adaptation to stress.