Adrenocorticotrophic hormone is a potent regulator of gene expression in human adrenal cells

The adrenal glands are the primary source of minerocorticoids, glucocorticoids and the so-called adrenal androgens. Under physiological conditions cortisol and adrenal androgen synthesis are controlled primarily by adrenocorticotrophic hormone (ACTH). Although it has been established that ACTH can stimulate steroidogenesis, the effects of ACTH on overall gene expression in human adrenal cells have not been established. In this study, we defined the effects of chronic ACTH treatment on global gene expression in primary cultures of both adult adrenal (AA) and fetal adrenal (FA) cells. Microarray analysis indicated that 48 h of ACTH treatment caused 30 AA genes and 84 AA genes to increase by greater than 4-fold, with 20 genes common in both cell cultures. Among these genes were six encoding enzymes involved in steroid biosynthesis, the ACTH receptor and its accessory protein, MRAP (ACTH receptor accessory protein). These data provide a group of ACTH-regulated genes including many that have not previously been studied with regard to adrenal function. These genes represent candidates for regulation of adrenal differentiation and steroid hormone biosynthesis.