Cortical-chromaffin cell interactions in the adrenal gland

Adrenal catecholamines and steroids are important regulators of the stress response, immune function, blood pressure, and energy homeostasis. Historically, the two cell populations within the adrenal gland-the steroid-producing adrenocortical cells and the catecholamine-producing chromaffin cells-have been regarded as two independent endocrine systems. Research on adrenal physiology and pathophysiology has therefore largely focused on the individual understanding of each cell type. However, adrenal cortex and medulla appear to be interwoven and show multiple contact zones without separation by connective tissue or interstitial membranes. In vitro studies, animal models, and the analysis of human adrenal pathophysiology have demonstrated critical importance of cortical-chromaffin crosstalk for adrenal function and disease. Thus, chromaffin cells regulate steroid-hormone release by the adrenal cortex and steroids induce catecholamine production in the medulla. Consequently, disorders of the adrenal cortex have been shown to affect chromaffin cell function and vice versa. Mouse models of adrenal cortical dysfunction, such as the targeted disruption of the 21-hydroxylase- or the CRHR1 genes, show alterations in chromaffin cell function, while disruption of tyrosine hydroxylase, a key enzyme in catecholamine synthesis, impairs adrenal cortical function. Accordingly, patients with congenital adrenal hyperplasia (CAH) and Addison's disease show reduced catecholamine biosynthesis. Immense progress in characterizing the mechanisms of chromaffin-cortical interactions has been achieved in recent years. Here, we summarize the current view on intraadrenal communication with respect to adrenal pathophysiology.