Compartmental arrangement of steroid precursors and the control of steroid hormone secretion in rat adrenal tissue in vitro.

Abstract

ABSTRACT Using a technique of incubation with dialysis, capsules (zona glomerulosa) and inner zone preparations of adrenal tissue from control, cortisol treated and Frusemide treated rats have been studied. The formation of corticosterone, deoxycorticosterone and 18-hydroxydeoxycorticosterone from both endogenous precursors and from added [14C] progesterone was examined. In the inner zone incubations from control and cortisol treated rats, products from the two precursor types appeared to be quite miscible as judged by their dialysability. Cortisol treatment depressed the formation of all three products from endogenous precursors, while their formation from [14C] progesterone was unaffected. These findings are consistent with the conventional view of the major point of action of ACTH at a stage preceding pregnenolone formation. In contrast, the formation of corticosterone from endogenous precursors in the capsule was specifically depressed by cortisol treatment. The formation of deoxycorticosterone and 18-hydroxydeoxycorticosterone was unaffected; the yields of all three compounds from [14C] progesterone was also unaffected. At the same time the dialysibility of the material formed from endogenous precursors was greatly reduced, while the dialysibility of the radioactive products was unchanged. In the Frusemide treated animals, capsule incubations showed no changes in formation of steroids from either precursor type and the miscibility of the steroid from the two sources was unaffected. In the inner zone incubations the formation of deoxycorticosterone and corticosterone was increased from both precursors, while the formation of 18-hydroxydeoxycorticosterone was reduced from endogenous precursors and unchanged from [14C] progesterone. Dialysibility of the steroids was unaffected by these procedures. The results suggest that various mechanisms may operate to allow independent variations in secretion rates of compounds occurring after the point of pregnenolone formation – normally held to be the major point of ACTH action. In particular it appears that, when ACTH secretion is suppressed, steroid formed from endogenous precursors may become attached to a non-dialysable component in the capsule of the gland. It is an attractive hypothesis that this renders the steroid less vulnerable to 11β-hydroxylation although it remains vulnerable to 21- and 18-hydroxylation. This mechanism is not observed if products from [14C] progesterone are studied alone. Treatment with Frusemide shows that other mechanisms may also allow differential changes in secretion rates of the three compounds. These mechanisms await elucidation.