Functional zonation of the guinea pig adrenal cortex: differences in mitochondrial steroid metabolism between the inner and outer zones.

Previous studies established that cells isolated from the chromatically distinct inner (primarily zona reticularis) and outer (zona fasciculata + zona glomerulosa) zones of the guinea pig adrenal cortex had vastly different steroidogenic capabilities; the outer zone produced far more cortisol than the inner zone. The mechanism(s) responsible for those differences were investigated by comparing mitochondrial steroid metabolism in the inner and outer zones. Cytochrome P-450 concentrations were similar in the two zones, but 11 beta-hydroxylase activity was approximately twice as great in the outer zone. More importantly, cholesterol sidechain cleavage, the rate-limiting step in steroidogenesis, was nearly 10 times greater in outer than inner zone mitochondria. Free cholesterol concentrations were also far higher in outer zone mitochondria. The results suggest that the relatively low level of steroid secretion by cells of the zona reticularis is attributable, at least in part, to deficiencies in mitochondrial cholesterol content and/or metabolism.