CONTEXTThe orphan nuclear receptor DAX-1 is essential for human adrenal cortex development and functions as a transcriptional repressor of multiple genes implicated in steroidogenic pathways.OBJECTIVEThe aim of this study was to investigate the localization of the DAX-1 protein in human fetal adrenal glands and to assess whether this protein can be modulated by the extracellular matrix and hormones.RESULTSDAX-1 is localized mainly in the nucleus in the outer definitive zone and in the cytoplasm in the fetal zone, whereas the number of DAX-1 positive cells decreases from the external to the internal portion of the gland. When cultured on a collagen or a fibronectin matrix, DAX-1 is localized in the nucleus of the definitive cells and exhibits a nucleocytoplasmic distribution in the fetal cells. ACTH stimulation induces nuclear localization of DAX-1 in fetal cells cultured on collagen without modifying nucleocytoplasmic localization on fibronectin. In contrast, angiotensin II induces the protein to be localized only in the cytoplasm in fetal cells cultured on either collagen or fibronectin.CONCLUSIONSThe localization of DAX-1 is compatible with the known functional properties of DAX-1 regarding the steroidogenic activity of adrenal cells. Moreover, this study suggests that modulation of DAX-1 localization in the fetal adrenal gland by hormones and components of the extracellular matrix may represent a mechanism for controlling the expression of steroidogenic enzymes in the definitive and fetal zones.