Aromatase in human fetal tissues

Abstract

The placenta has been shown to be the major source of estrogen production during pregnancy. This investigation was undertaken to compare the content and activity of aromatase in the placenta and various other human fetal tissues. Tissues were obtained from first- and second-trimester human abortuses. The amount of aromatase P-450 (aromatase cytochrome P-450) in tissue homogenates was determined after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting by use of a polyclonal antibody directed against aromatase cytochrome P-450. The activity of aromatase in microsomal preparations was assayed by determining the rate of incorporation of tritium from 1-[3H]androstenedione into [3H]water. The greatest amount of aromatase cytochrome P-450 (55 kd) was detected in placenta and lesser amounts were detected in other tissues. Aromatase activity also was highest in placental microsome fractions (368 +/- 62.4 pmol/mg/hr [mean +/- SE], n = 9). A significant amount of aromatase activity was also detected in fetal liver (19 +/- 4.8 pmol/mg/hr, n = 7). Much less activity was found in brain (2.8 +/- 1.0 pmol/mg/hr, n = 6) and intestine (2.7 +/- 1.3 pmol/mg/hr, n = 7). Minimal activity was noted in adrenal (n = 5), spleen (n = 4), stomach (n = 4), and muscle (n = 5) (1.2 to 1.5 pmol/mg/hr). Activity in kidney (n = 7), heart (n = 4), and lung (n = 4) was extremely low (less than 0.8 pmol/mg/hr). In conclusion, the placenta is a major site of conversion of C19 steroid precursors to estrogens because of the amount of enzyme and the high rate of activity of aromatase compared with those of other fetal tissues. However, considering the size and rate of aromatase activity in other fetal tissues such as liver, brain, and intestine, these tissues also may contribute to the total estrogen production in the fetal-placental unit.