THE EFFECTS OF DIABETES ON PLACENTAL AROMATASE-ACTIVITY

Diabetes complicates 2-3% of all pregnancies and is associated with an increase in both perinatal morbidity and mortality, though reasons fo r these adverse outcomes are unknown. Estrogen biosynthesis is a criti cal factor during pregnancy and is carried out in the placenta via aro matase (cytochrome P450 19A1), which catalyzes the conversion of C-19 androgens to C-18 estrogens. Previous studies have shown that hormones such as insulin-like growth factors and insulin regulate aromatase ac tivity when studied in vitro. Interestingly, levels of these hormones are altered in patients with diabetes. Thus, we hypothesized that the presence of maternal diabetes may alter placental aromatase activity a nd thus estrogen biosynthesis, possibly serving as one factor in the a dverse outcomes of babies born to mothers with diabetes. To this end, we measured the production of 19-hydroxyandrostenedione, 19-oxoadroste nedione and estrone in 30 placental tissues from diabetic patients, us ing [7-H-3]androst-4-ene-3,17-dione as a model substrate for aromatase (P450 19A1). A statistical difference was detected in the percentage of 19-oxoandrostenedione formed between the overt and control groups ( P < 0.05). Additionally, NADPH P450-reductase levels were measured in these same tissues to determine whether alterations in this enzyme nec essary for aromatase activity could be affected by diabetes. No differ ences in reductase levels were detected among the patient groups. Howe ver, a statistical correlation was found between NADPH P450-reductase activity and the formation velocities of all three estrogen products ( P < 0.05), Thus, it appears that the presence of diabetes does not aff ect placental aromatase activity. (C) 1997 Elsevier Science Ltd. All r ights reserved.