Review of studies on estrogen biosynthesis in the human.

While the gonads and placenta are usually thought of as the principal sites of estrogen synthesis, many other tissues are now known to contain the aromatase enzyme. Despite a wealth of information, the functional significance, if any, of this wide-spread distribution is not yet clear. Nonetheless, elevated estrogen production resulting from either an apparent increase in enzyme activity or increased substrate availability in blood can have important effects on target tissues such as the breast, uterus, and bone. Our early studies suggesting that aromatase inhibitors can effectively reduce the impact of peripheral estrogen synthesis have been amply confirmed by the elegant studies of Santen and others. Many previous studies have suggested that aromatase activity may be present in breast tumors. The profound implications for growth of estrogen-sensitive tumors led us to reevaluate this question. Using a sensitive modification of our original radiometric aromatase assay, we have found detectable activity in only about 40% of human breast tumors (n = 100). Only rarely (1/100) does the aromatase activity exceed 1.0 pm/hr/g tissue or 0.001% of that found in the human placenta. These quantitative results contradict several published reports which suggest that most breast tumors contain biologically significant levels of aromatase activity.