Human Reproduction, Vol 12, 1890-1896, Copyright © 1997 by Oxford University Press
E Pierro, CL Andreani, N Lazzarin, R Cento, A Lanzone, A Caruso and S Mancuso
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.
ARTICLES
Further evidence of increased aromatase activity in granulosa luteal cells from polycystic ovary
Department of Obstetrics and Gynecology, Universita Cattolica del Sacro Cuore, Roma, Rome, Italy.
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