The Mechanism of Action of Adrenocorticotropic Hormone

This chapter discusses the relationship of the structure of adrenocorticotropic hormone (ACTH) to its function and the pathway of adrenal cortical biosynthesis. A series of remarkable achievements in protein chemistry have led to the isolation and purification of ACTH, the determination of its primary structure, and its synthesis. The biochemical synthesis of adrenal corticosteroids with its many complexities is explained in the chapter. The influence of ACTH on the adrenal cortex is not limited to the stimulation of corticosteroid production; the maintenance of the structure of the adrenal cortex is also dependent upon this hormone. The removal of the pituitary gland from rats resulted in the atrophy of the adrenal cortex and that the transplantation of the pituitary to hypophysectomized animals caused a return of adrenal cortical weight toward normal. The synthesis of glucocorticoids in the adrenal cortex is accomplished by a series of enzymes situated in different organelles. The evidence indicates that the first substrate, cholesterol, enters the mitochondrion where it is transformed into pregnenolone. Pregnenolone leaves the mitochondrion and is converted into progesterone in the cytoplasm. Progesterone, in turn, is transformed into deoxycorticosterone by an enzyme system in the microsomal fraction of the cell. Corticosterone is produced finally from deoxycorticosterone that has reentered the mitochondrion.