Effects of clofibrate on the metabolism of progesterone and oestradiol in rat liver microsomal fraction.
Effects of clofibrate on the metabolism of progesterone and oestradiol in rat liver microsomal fraction.
复制标题
安妥明对大鼠肝微粒体组分中孕酮和雌二醇代谢的影响。
作者：
K. Einarsson;J. Gustafsson;K. Hellström
1.在与对照组和氯贝酸治疗组大鼠的肝微粒体部分孵育期间，[4-（14）C]孕酮和[4-（14）C]雌二醇的底物转化率分别约为10- 15%和20-25%。2.对照大鼠制备的孕酮代谢产物在16 α-位（14%）、6 β-位（12%）和2 α-位（7%）发生羟基化。在雌二醇形成的产物中，12%作为16 α-羟基化衍生物回收，而5%具有6 β-羟基，2%具有6 α-羟基。3.氯贝特影响孕酮和雌二醇的微粒体代谢。它诱导了两种化合物的7 α-羟基化，在对照大鼠中未发现代谢转化。孕酮的6 β-羟基化和雌二醇的6 α-羟基化分别增强2倍和3.5倍。孕酮的2 α-羟基化、20 α-和20 β-羟基类固醇还原显著降低，雌二醇的16 α-和6 β-羟基化也显著降低。
1. The substrate conversion of [4-(14)C]progesterone and [4-(14)C]oestradiol during incubation with the liver microsomal fraction from both control and clofibrate-treated rats amounted to about 10-15 and 20-25% respectively. 2. The metabolites of progesterone formed by preparations from control rats were hydroxylated in the 16alpha-position (14%), the 6beta-position (12%) and the 2alpha-position (7%). Of the products formed from oestradiol 12% were recovered as a 16alpha-hydroxylated derivative whereas 5% had a 6beta- and 2% a 6alpha-hydroxyl group. 3. Clofibrate affected the microsomal metabolism of both progesterone and oestradiol. It induced 7alpha-hydroxylation of both compounds, metabolic conversions not found in control rats. The 6beta-hydroxylation of progesterone and the 6alpha-hydroxylation of oestradiol were enhanced by a factor of 2 and 3.5 respectively. The 2alpha-hydroxylation, and the 20alpha- and 20beta-hydroxy steroid reduction of progesterone were significantly decreased as were the 16alpha- and the 6beta-hydroxylation of oestradiol.