Human steroidogenesis, showing<unk> -α hydroxylase at upper center, with pathways to aldosterone and cortisol at right, and pathways to androgens at left. The enzyme P450c21, commonly referred to as<unk> -hydroxylase <unk> -OH), is embedded in the smooth endoplasmic reticulum of the cells of the adrenal cortex. It catalyzes hydroxylation of 17α-hydroxyprogesterone (17OHP) to 11-deoxycortisol in the glucocorticoid pathway, which starts from pregnenolone and finishes with cortisol. It also catalyzes hydroxylation of progesterone to 11-deoxycorticosterone (DOC) in the mineralocorticoid pathway on its way from pregnenolone to aldosterone. Deficient activity of this enzyme reduces the efficiency of cortisol synthesis, with consequent hyperplasia of the adrenal cortex and elevation of ACTH levels. ACTH stimulates uptake of cholesterol and synthesis of pregnenolone. Steroid precursors up to and including progesterone, 17α-hydroxypregnenolone, and especially 17α-hydroxyprogesterone accumulate in the adrenal cortex and in circulating blood. Blood levels of 17OHP can reach 10-1000 times the normal concentration. Since<unk> -hydroxylase activity is not involved in synthesis of androgens, a substantial fraction of the large amounts of 17α-hydroxypregnenolone is diverted to synthesis of DHEA, androstenedione, and testosterone beginning in the third month of fetal life in both sexes. Synthesis of aldosterone is also dependent on<unk> -hydroxylase activity. Although fetal production is impaired, it causes no prenatal effects, as the placental connection allows maternal blood to "dialyze" the fetus and maintain both electrolyte balance and blood volume.
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency
Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency
Congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency
Primary pigmented nodular adrenocortical disease
Lipoid congenital adrenal hyperplasia
Cortisone reductase deficiency
Pituitary ACTH hypersecretion