Steroidogenic Properties of a New Aldosterone-Stimulating Factor: Interaction with Angiotensin II and Adrenocorticotropin during Variations of Dietary Sodium*

We investigated the in vitro steroidogenic activity of a new aldosterone-stimulating factor (ASF). Aldosterone responses of adrenal zona glomerulosa cells to ASF were assessed in response to variations in sodium intake and during incubation with either ACTH or angiotensin II (AII). Studies were performed in collagenase-dispersed adrenal capsular cells harvested from male New Zealand White rabbits that were on either regular or low sodium diets for 7-10 days. ASF, AII, and ACTH produced dose-dependent increases in aldosterone production. In cells from sodium-replete rabbits, the concentrations required to elicit the half-maximum response (ED50) were 2.2 +/- 0.3 (+/-SE) X 10(-11), 7.2 +/- 1.1 X 10(-10), and 3.4 +/- 0.5 X 10(-8) M for ACTH, AII, and ASF, respectively. Sodium depletion increased maximal responses but not sensitivity to AII and ACTH; responses to ASF were essentially unchanged. Large concentrations of ASF (10(-7) M) potentiated AII-induced aldosterone responses of adrenal capsular cells from sodium-depleted, but not sodium-replete, rabbits. In marked contrast, similar concentrations of ASF inhibited ACTH-induced aldosterone production of adrenal capsular cells from both sodium-replete and sodium-depleted rabbits. It is concluded that ASF has its own intrinsic steroidogenic activity. Furthermore, although large concentrations of ASF potentiate AII responses in sodium-depleted animals, ASF inhibits the aldosterone-stimulating activity of ACTH in both sodium-replete and sodium-depleted animals.