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Muratori, M; Lippi, A; Mancina, R; Iafrate, E.M; Cirillo, R; Lopez, G; Bigioni, M; Maggi, M; Criscuoli, M; Maggi, C.A
The Journal of steroid biochemistry and molecular biology, 04/2003, Letnik: 84, Številka: 5Journal Article
MEN 11066 is a new non-steroidal compound which potently inhibits human placenta ( K i=0.5 nM) and rat ovarian ( K i=0.2 nM) aromatase in vitro. In vivo, a single oral dose of 0.3 mg kg −1 significantly decreased uterus weight in immature rats after stimulation of uterus growth by androstenedione. MEN 11066 reduced in a dose-dependent manner plasma estradiol levels in adult female rats treated with pregnant mare serum gonadotropin (PMSG). After 2 weeks of repeated daily treatment in adult rats, a significant decrease in uterine weight was observed together with a 65% decrease in plasma estradiol, whereas plasma levels of testosterone, progesterone, aldosterone, corticosterone, cholesterol, LH and FSH were not affected. The lack of any effect by MEN 11066 on adrenal steroids was confirmed by the unchanged plasma corticosterone and aldosterone levels in immature rats and also in adult rats when the repeated treatment with MEN 11066 (15 days) was followed by the administration of a synthetic ACTH analogue. No change in 11β-hydroxylase or 21-hydroxylase activities was produced in vitro by the addition of 10 μM MEN 11066. Fifteen-day treatment with MEN 11066 did not produce changes in several rat hepatic enzymatic activities involved in the metabolism of xenobiotics. These results demonstrated that MEN 11066 is a potent inhibitor of aromatase which does not interfere with the cytochrome P450 involved in the synthesis of other steroids or in the metabolism of xenobiotics.
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