21-Hydroxylase

Look first to the fetal adrenal, then the fetoplacental unit, then the mother, and only rarely an androgen-producing gonad.

The most common cause is 21-hydroxylase deficiency.

CYP21A2 deficiency blocks cortisol synthesis.

ACTH rises.

Precursors accumulate.

Now add POR.

P450 oxidoreductase supplies electrons to several microsomal cytochrome P450 enzymes, including CYP17A1, CYP21A2, and aromatase.

So POR deficiency does not produce one clean block.

It perturbs several reactions at once.