MATURATIONAL CHANGES IN STEROIDOGENESIS IN THE INNER AND OUTER ZONES OF THE GUINEA-PIG ADRENAL-CORTEX

Studies were done to determine the effects of age on steroidogenesis i n the inner (zona reticularis) and outer (zona fasciculta plus glomeru losa) zones of the guinea pig adrenal cortex. In 35-day-old animals, c ortisol production by adrenal outer zone cells was approximately twice as great as that by inner zone cells. With aging, cortisol secretion by inner zone cells decreased to very low levels, but there was no det ectable change in the capacity for cortisol production by the outer zo ne. However, the outer zone comprised a progressively decreasing fract ion of the total adrenal mass in older animals. To determine the basis for the decline in cortisol production by inner zone cells with aging , the activities of several steroidogenic enzymes were determined. Mic rosomal 21-hydroxylase activity was greater in the inner than outer zo ne but was not significantly affected by age. By contrast, 17alpha-hyd roxylase activity was greater in the outer zone at all ages, and decre ased with aging in the inner but not the outer zone. Mitochondrial cho lesterol sidechain cleavage and 11beta-hydroxylase activities were als o higher in the outer than inner zone and declined in the inner zone o nly in older animals. The decrease in inner zone cholesterol sidechain cleavage activity with aging was proportionately greater than the age -dependent changes in other enzyme activities. The results indicate th at the effects of aging on steroidogenesis are both zone- and enzyme-s pecific. The overall decline in cortisol secretion by the guinea pig a drenal cortex with aging is attributable to both a decrease in cortiso l production by the cells of the zone reticularis and a disproportiona te increase in the mass of the gland comprised by this zone. The decre ase in cortisol secretion correlates closely with a decline in cholest erol sidechain cleavage activity in the zona reticularis, and may be c ausally related.