Physiological and pathological effects of steroids on the function of the adrenal cortex

The adrenal cortex is the site of the synthesis of steroid hormones such as the glucocorticoid cortisol and the mineralocorticoid aldosterone. The pathway of biosynthesis of these steroids from cholesterol involves a sequence of transformations using cytochrome P-450 enzymes which varies within the adrenal cortex as a result of the differential localization of enzymes within the zones. The hypothesis presented here is that as a result of the arrangement of the vasculature in the adrenal gland, high concentrations of steroids may be expected to accumulate and may have autoregulating effects. These may include the following: (1) the normal morphological and functional zonation of the adrenal cortex may be regulated by gradients of steroids in the adrenal cortex; (2) destruction of cytochrome P-450 enzymes on interaction with certain steroids which act as pseudosubstrates may form part of the pathogenesis of some steroidogenic enzyme deficiencies. Under normal conditions, the individual cytochrome P-450s are not rate-limiting for steroidogenesis. Under some pathological conditions, individual cytochrome P-450 enzyme activities may become rate-limiting, with consequent overproduction of precursor steroids, leading to mineralocorticoid or androgen excess.