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21-Hydroxylase (P450c21)

المؤلف:  Norman, A. W., & Henry, H. L.

المصدر:  Hormones

الجزء والصفحة:  3rd edition , p47

2026-06-18

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The 21-hydroxylation of steroids is essential to the conversion of both progesterone to deoxycorticosterone (DOC) in the zona glomerulosa (mineralocorticoids) and 17-hydroxy-progesterone to 11-deoxycortisol in the zona fasciculata (glucocorticoid). See Figure 1 for the steps of steroid metabolism in the zona glomerulosa and zona fasciculata, and entry 3 in Table1. The P450c21 is found in the endoplasmic reticulum. Evidence has been presented that humans have two genes coding for P450c21. The details of the expression of these genes are clinically very important since approximately 1 in 15,000 live births have a 21-hydroxylase deficiency characteristic of congenital adrenal hyperplasia (CAH); this P450c21 mutation constitutes as many as 90% of all CAH patients. A detailed discussion of this topic is beyond the scope of this chapter.

Fig1. Adrenal cortex pathways for production of three classes of steroid hormones. Cholesterol and the presence of the cholesterol side chain cleavage enzyme are the starting point of separate steroid hormone(s) biosynthesis for the three classes. The zona glomerulosa (mineralocorticoids) produces aldosterone. A structural hallmark of aldosterone is the presence of both a C-11 hydroxyl and a C-18 aldehyde. The C-18 aldehyde can form either a five member hemiacetal ring, which uses the C-11 hydroxyl group or a six member hemiacetal ring, which uses the C-21 hydroxyl group. These are reminiscent of carbohydrate chemistry. The zona fasciculata (glucocorticoids) produces both cortisol and corticosterone. The zona reticularis produces limited amounts (represented by the dashed arrow) of the androgens, dehydroepiandrosterone (DHEA), androst-4-ene-3,17-dione and testosterone. DHEA can be converted to DHEA-sulfate via a sulfotransferase, which forms a mixed ester with the 3β-hydroxyl group. For each of the steroid enzyme transformations, the 3-7 letter/number acronymn is shown in magenta next to the arrow. The enzyme’s full name for each acronymn is tabulated in Table 1.

Table1. ^a Key Human Enzymes Concerned with the Production of Steroid Hormones