ADRENAL STEROIDOGENESIS AND REGULATION

The adrenal cortex produces three main types of hormones under the control of independent regulatory systems: glucocorticoids (cortisol), mineralocorticoids (aldosterone) and androgens (testosterone). The cortex is divided into three distinct zones -- the outer zona glomerulosa, the middle zona fasciculata, and the inner zona reticularis. The synthesis of cortisol occurs in the zona fasciculata of the cortex, while the mineralocorticoid aldosterone is dependent upon enzymatic activity limited to the zona glomerulosa. Sex steroids are synthesized in the zona reticularis. Figure 1 is a schematic diagram of steroidogenesis in the adrenal cortex.

Figure 1. Schema of adrenal steroidogenesis. (1)

Cortisol is synthesized under the trophic control of adrenocorticotropic hormone (ACTH), forming a negative feedback loop in which high serum cortisol centrally inhibits and low serum cortisol stimulates release of ACTH, which defines the hypothalamic-pituitary-adrenal axis. Net ACTH release has basal, diurnal, and stress induced components. The pulsatile release of ACTH is in turn modulated by corticotropin releasing hormone (CRH), while the central nervous system determines the hypothalamic set point for the expected plasma cortisol level. A deficiency of 21-hydroxylase impairs production of cortisol resulting in increased pituitary secretion of ACTH. Chronic elevations of ACTH levels stimulate the accumulation of precursor steroids in the impeded pathways and cause excessive steroid synthesis in other adrenal biosynthetic pathways unaffected by the enzyme deficiency.