Comparisons of Adrenocortical Cell Lines as In Vitro Test Systems
The adrenal gland is a compound endocrine organ separated into two distinct, developmentally unrelated tissues-an adrenal medulla and an adrenal cortex. The adrenal medulla is the core of the adrenal gland; the chromaffin cells of the medulla are the body’s main source of the catecholamines. The cells comprising the adrenal cortex are derived from mesoderm of the dorsal coelomic wall and thus have common features to the steroidogenic cells within the gonads. In 1866, Arnold first described the histology of the adrenal cortex and noted that it was divided into three concentric zones which he named the zona glomerulosa, zona fasciculata, and zona reticularis (Arnold, 1866). While this description was based on the histological organization, it is now accepted that these zones have functionally distinct roles in steroid hormone production. Namely, the glomerulosa synthesizes mineralocorticoids, the fasciculata produces glucocorticoids, and in the human, the zona reticularis produces C19 steroids, including DHEA and DHEA-sulfate. Molecular mechanisms leading to zone specific expression of these steroids are yet to be defined. Each adrenocortical zone synthesizes its steroid products from the common substrate cholesterol. Steroidogenic cholesterol can arise from endogenous cholesterol stores, from serum derived lipoprotein or from de novo synthesis. Within the human adrenal cortex, steroid synthesis involves coordinated actions of five forms of cytochrome P450 and the enzyme 3-hydroxysteroid dehydrogenase (Figure 1); these enzymes are distributed between the mitochondria and the
Figure 1 Human adrenal steroid biosynthetic pathways illustrating the three main products of the adrenal (aldosterone, cortisol, and DHEA/S) and the enzymes that synthesize these products. Classification for the enzymes in the P450 superfamily follow the guidelines previously reported (Nelson et al., 1996). Abbreviations: StAR, steroidogenic acute regulatory protein; CYP11A1, cholesterol side-chain cleavage; CYP17, 17-hydroxylase 17,20-lyase; SULT2A1, DHEA-sulfotransferase; HSD3B2, 3-hydroxysteroid dehydrogenase type II; CYP21, 21-hydroxylase; CYP11B1, 11-hydroxylase; CYP11B2, aldosterone synthase.