Figure 1.

Human and rodent adrenal steroidogenic pathways. In the adrenal, upon stimulation, cholesterol esters (CE) from the LDL endocytic pathway (human) or the SR-B1 selective pathway (rodents) are hydrolyzed by hormone-sensitive lipase (HSL) to release free cholesterol (FC) as the common precursor for steroidogenesis. FC, which can also be synthesized de novo within the ER, traffics to the outer mitochondrial membrane and is then transported into the inner mitochondrial membrane by StAR, where it is cleaved by CYP11A to pregnenolone, a common precursor for all other steroid hormones. The adrenal cortex is the site of steroid hormone synthesis and different steroidogenic enzymes are expressed in cells located within different zones of the adrenal cortex, resulting in different classes of steroid hormones being released from different layers. The cells of the zona glomerulosa synthesize aldosterone, the cells of the zona fasciculata synthesize cortisol, and the cells of the zona reticularis produce androgens. In rodents, there is a very low level of CYP17; consequently, corticosterone is the dominant glucocorticoid produced.