STUDIES ON THE MECHANISM OF SECRETION OF CORTICOSTEROIDS BY THE ISOLATED PERFUSED ADRENAL OF THE RAT

A technique for the perfusion of the rat adrenal cortex is described. With tissue culture Medium 199 the preparation was responsive in terms of steroid production to both ACTH and K+ ions. Production of corticosterone and 18-hydroxydeoxycorticosterone (18-hydroxy-DOC) was stimulated by ACTH when it was administered at rates between 5 μu./min and 5 mu./min. Increasing the K+ ion concentration of the perfusate from 3·6 to 5·4 and 8·9 mmol/l stimulated the production of aldosterone, 18-hydroxycorticosterone and deoxycorticosterone, although not of corticosterone or 18-hydroxy-DOC. This preparation has been used to study further the mechanism of secretion of corticosterone and 18-hydroxy-DOC. Thus, production of these two steroids was measured at different perfusion flows, varying between 0·1 and 0·6 ml/min, with different levels of ACTH stimulation. Corticosterone production was significantly (P < 0·001) increased by increasing flows both under control conditions and when ACTH was administered at constant rates of 50 μu./min or 1 mu./min. Production of 18-hydroxy-DOC was not affected by flow either under control conditions or with 50 μu. ACTH/min. However, when ACTH was administered at 1 mu./min, 18-hydroxy-DOC production was also significantly (P < 0·001) increased by flow. The results are consistent with those obtained in previous in-vitro studies and have been interpreted as suggesting that the main mechanism of corticosterone secretion is simple diffusion. In contrast, 18-hydroxy-DOC secretion, at least at sub-maximal levels of stimulation, appears to require a more complex process.