ACTH acts on the adrenal gland by binding to a specific receptor in the membrane of the cell (Fig. 7.4). This results in the stimulation of the membrane-bound adenylate cyclase enzyme, leading to rapid production of intracellular cyclic AMP (cAMP), a mechanism that may also involve calcium entry into the cell. Other cyclic nucleotides such as cGMP may also be important. cAMP, in turn, activates a protein kinase (by dissociating an active subunit), which then stimulates a number of protein-phosphorylation processes using ATP. The role of the phosphoproteins that are formed is not yet clearly defined, but they appear to mediate cholesterol ester hydrolysis and side-chain cleavage of cholesterol to form pregnenolone. The increased concentration of pregnenolone subsequently leads to increased biosynthesis of cortisol and the androgens.
