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 normal ovaries. Treatment with atamestane (10 micromol/l) determined a strong inhibition of basal aromatase activity in both types of cells; however, its effect was markedly more pronounced in granulosa cells from normal ovary than in granulosa cells from polycystic ovaries (PCO; P < 0.01). Concomitant treatment with insulin (25 microg/ml) and increasing doses of atamestane (0.01-10 micromol/l) caused a dose-dependent inhibition of insulin-stimulated aromatase activity, but again with marked differences between the two types of cells. In granulosa cells from PCO, the minimal effective dose of atamestane was 1 micromol/l and it had an EC50 of 2.23 +/- 0.4 micromol/l and a maximal inhibitory effect of 75%; in granulosa cells from normal ovary, the minimal effective dose of atamestane was 0.01 micromol/l, the EC50 was 0.4 +/- 0.07 micromol/l, and the maximal inhibitory effect was 94%. Significant differences were observed between the different cells at all the studied dose points. Reversibility studies showed that resumption of aromatase activity in granulosa cells from PCO is basally greater and more inducible with insulin treatment. This study provides further evidence of an increased in-vitro function of the aromatase complex in granulosa cells from PCO, that could be induced by an altered cellular autoregulation.
Pierro
E
E
Department of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, Roma, Rome, Italy.
Andreani
C L
CL
Lazzarin
N
N
Cento
R
R
Lanzone
A
A
Caruso
A
A
Mancuso
S
S
D000328:Adult; D000735:Androstenedione / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors; D002452:Cell Count; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008184:Luteal Cells / Q000187:drug effects / Q000201:enzymology*; D011085:Polycystic Ovary Syndrome / Q000201:enzymology*; D011374:Progesterone / Q000096:biosynthesis
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D007328:Insulin; D000735:Androstenedione; D011374:Progesterone; C048751:atamestane; D001141:Aromatase