The role of cytochrome P450 enzymes of the adrenal cortex in the control of glucocorticoid and mineralocorticoid synthesis is being evaluated in rats and guinea pigs. Systems being examined include cholesterol side chain cleavage, steroid 11 and 18-hydroxylation, cholesterol ester hydrolase and aldosterone synthesis from corticosterone. A major project concerns the role of cytochrome P450 systems in the normal circadian rhythm of corticosterone secretion by the rat. Emphasis is being placed upon the supply of cholesterol to the cholesterol side chain cleavage system during stress and ACTH treatment. Experiments are designed to investigate the possibility that a pituitary factor other than ACTH is involved in the response of the rat adrenal cortex to stress. The possibility that ACTH action on steroidogenesis is mediated through phosphorylation of a rapidly-turning-over protein is being examined. An important approach to the examination of the effects of various agents on the adrenal cortex includes electron microscopic examination of the adrenal with the use of morphometric analysis.