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 of 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 uu.'/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 0.6ml/min, with different levels of ACTH stimulation. Corticosterone production was significantly (P less than 0.001) increased by increasing flows both under control conditions and with ACTH was administered at constant rates of 50 uu./min or 1 mu./min. Production of 18-hydroxy-DOC was not affected by flow either under control conditions or with 50 uu. ACTH/min. However, when ACTH was administered at 1 mu./min. 18-hydroxy-DOC production was also significantly (P less than 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.