Lobaccaro-Henri C, Saintot M, Laffargue F, Zahradnik H P, Descomps B, Thaler-Dao H
Unite 58 I.N.S.E.R.M., Montpellier, France.
Prostaglandins. 1992 Nov;44(5):443-55. doi: 10.1016/0090-6980(92)90139-k.
We studied the effect of antiprogesterone RU 486 on spontaneous uterine contractility and PGI2 release with human myometrial strips superfused "in vitro". A decrease of PGI2 release into the superfusion medium was observed after 20 min superfusion. The inhibition was dose-dependent and reversible. After 20 min washing with tyrode medium without RU 486, the uterine strips recovered their initial rate of release. R5020, a progesterone agonist, did not affect PGI2 release nor dexamethasone and testosterone. Parallel to the decrease of PGI2 observed during RU 486 superfusion, the uterine spontaneous contraction frequency decreased, while the amplitude and duration of contractions increased. The alteration of uterine contractility was also rapid, dose-dependent and reversible. Modification of uterine strip spontaneous contractility, similar to those induced by RU 486, were also observed with superfusions of R5020 at concentrations as low as 10(-9)M, dexamethasone (10(-8)M), but not with superfusions of testosterone. These observations are not in favour of a progesterone-receptor mediated effect of RU 486 in our model. The mechanism of action may be related to the antiprogesterone specific structure i.e. the bulky substituent at the C-11 position. The RU 486 effect on uterine strip contractility, mimicked by other steroids, could point to a non-specific lipid/membrane interaction. However, the fact that testosterone did not affect motility, may indicate a possible specificity of steroids having a 3 oxo pregnene structure.
我们在体外灌流的人子宫肌条上研究了抗孕激素RU 486对子宫自发收缩性和PGI2释放的影响。灌流20分钟后，观察到灌流培养基中PGI2释放减少。这种抑制作用呈剂量依赖性且可逆。用不含RU 486的台氏液冲洗20分钟后，子宫肌条恢复其初始释放速率。孕激素激动剂R5020、地塞米松和睾酮均不影响PGI2释放。与RU 486灌流期间观察到的PGI2减少同时发生的是，子宫自发收缩频率降低，而收缩幅度和持续时间增加。子宫收缩性的改变同样迅速、呈剂量依赖性且可逆。在低至10(-9)M的R5020、10(-8)M的地塞米松灌流时，也观察到子宫肌条自发收缩性的改变，类似于RU 486诱导的改变，但睾酮灌流时未观察到。在我们的模型中，这些观察结果不支持RU 486通过孕激素受体介导的作用。其作用机制可能与抗孕激素的特定结构有关，即C-11位的庞大取代基。RU 486对子宫肌条收缩性的作用被其他类固醇模拟，这可能表明存在非特异性的脂质/膜相互作用。然而，睾酮不影响运动性这一事实，可能表明具有3-氧代孕烯结构的类固醇存在可能的特异性。
