Comparative study of cyclic AMP-generation system, steroid biosynthesis and lipid metabolism in vitro in ACTH...

The responses of the cyclic AMP-generation system and corticosteroids biosynthesis to ACTH and angiotensin II and cholesterol and other lipid contents in adrenal tissues were estimated in the in vitro experiments in 3 cases of Cushing's syndrome due to ACTH-responsive and unresponsive adenomas, one case of Cushing's disease (diffuse hyperplasia), one case of primary aldosteronism and one normal subject. The responses of cAMP accumulation and corticosteroids production to ACTH in in vitro studies were quite in good agreement with the in vivo responses of plasma cortisol by ACTH infusion test. The adenylate cyclase activity decreased and the phosphodiesterase activity increased in the case of hyperplasia and in one case of ACTH-responsive adenoma, whereas the basal cyclic AMP content was slightly more in ACTH-responsive adenoma and maximal in hyperplasia compared with that of the normal adrenal tissue. The characteristic features observed in ACTH-unresponsive adenoma were the largest amount of the basal corticosteroids production and esterified cholesterol content, and the lowest content cAMP. These results indicate that there was not always the consistent correlation between the cAMP-generation system, corticosteroids and aldosterone production, and conversion of cholesterol to pregnenolone by the stimulation of ACTH and angiotensin II in adrenal tumors.