Cholesterol, the common precursor of all adrenal steroids, is a 27-carbon compound that originates from three sources (Fig. 72-5). Most cholesterol used in steroidogenesis is derived from the lysosomal degradation of circulating low-density lipoproteins. Cholesterol-rich low-density lipoprotein binds to specific
plasma membrane receptors on adrenocortical cells, is internalized by endocytosis, and is degraded to liberate free cholesterol. The cholesterol that is not used in steroidogenesis is esterified and stored within cytoplasmic vacuoles in the cortical cells. When additional steroid production is needed, the stored cholesterol esters are hydrolyzed by cytoplasmic enzymes to generate free cholesterol. Finally, adrenocortical cells produce some of their cholesterol by de novo synthesis from acetate.

The relative activities of the steroidogenic enzymes within a given steroid-secreting cell determine which secretory products that cell produces. For example, 17α-hydroxylase activity exists only in the zona fasciculata and reticularis. Therefore, cortisol and adrenal androgens cannot be synthesized by the zona glomerulosa.

All of the precursors to the major adrenal biosynthetic products are measurable in the peripheral circulation. Because steroid hormones cannot be stored in steroidogenic cells, they are secreted immediately after their biosynthesis. Cortisol, 11-deoxy-cortisol, aldosterone, corticosterone, and 11-deoxycorticosterone are derived almost exclusively from adrenal whereas most other steroids are derived from a combination of adrenal and gonadal sources. Table 72-3 gives representative values for the production rates, basal plasma concentrations, and relative adrenal contribution to the blood production rate for the principal steroids of adrenal origin.