Biochemical mechanism of aromatization.

The aromatization of androgens to estrogens by placental aromatase involves three hydroxylations which take place in sequence. The first two occur at the C-19-methyl group while the site of the final and rate-determining hydroxylation has been identified as being at 2 beta. The product of this reaction collapses to estrogen by a rapid nonenzymatic mechanism. The absence of a direct relationship between the enzyme(s) responsible for estrogen formation and the end product results in an absence of product feedback inhibition, a consequence with potential physiological implications. The proposed mechanism of estrogen formation is supported by chemical, biochemical, and immunological evidence.