FURTHER EVIDENCE OF INCREASED AROMATASE-ACTIVITY IN GRANULOSA-LUTEAL CELLS FROM POLYCYSTIC OVARY

This study evaluated the effect of atamestane (a competitive inhibitor of P-450 aromatase) on granulosa luteal cells from polycystic and nor mal ovaries, Treatment with atamestane (10 mu mol/l) determined a stro ng inhibition of basal aromatase activity in both types of cells; howe ver, its effect was markedly more pronounced in granulosa cells from n ormal ovary than in granulosa cells from polycystic ovaries (PCO; P < 0.01). Concomitant treatment with insulin (25 mu g/ml) and increasing doses of atamestane (0.01-10 mu mol/l) caused a dose-dependent inhibit ion of insulin-stimulated aromatase activity, but again with marked di fferences between the two types of cells, In granulosa cells from PCO, the minimal effective dose of atamestane was 1 mu mol/l and it had an EC50 of 2.23 +/- 0.4 mu mol/l and a maximal inhibitory effect of 75 % ; in granulosa cells from normal ovary, the minimal effective dose of atamestane was 0.01 mu mol/l, the EC50 was 0.4 +/- 0.07 mu mol/l, and the maximal inhibitory effect was 94%, Significant differences were ob served between the different cells at all the studied dose points, Rev ersibility studies showed that resumption of aromatase activity in gra nulosa cells from PCO is basally greater and more inducible with insul in treatment, This study provides further evidence of an increased in- vitro function of the aromatase complex in granulosa cells from PCO, t hat could be induced by an altered cellular autoregulation.