Decreased liver cytochrome P-450 in rats caused by norethindrone or ethynyloestradiol.
Decreased liver cytochrome P-450 in rats caused by norethindrone or ethynyloestradiol.
复制标题
炔诺酮或乙炔雌二醇引起大鼠肝细胞色素 P-450 降低。
作者：
I. White;U. Muller
1.19-Nor-17alpha-pregna-1，3，5(10)-trien-20-yne-3，17-diol(乙炔雌二醇)或17beta-hydroxy-19-nor-17alpha-pregn-4-en-20-yn-3-one(去甲肾上腺素)，而不是17alpha-ethyl-17beta-hydroxy-19-norandrost-4-en-3-one(去甲肾上腺素)，在体外与大鼠肝微粒体和NADPH产生系统孵育时，可引起细胞色素P-450的时间依赖性丢失。2.催化去甲肾上腺素介导的细胞色素P-450丢失的酶系统具有微粒体混合功能氧化酶的许多特征。它需要NADPH和空气，并被Co抑制，但不受1 mM化合物SKF 525A的影响。3.与对照组相比，苯巴比妥钠处理组大鼠微粒体中去甲肾上腺素介导的细胞色素P-450丢失明显增加。用3β-羟基-孕酮-5-烯-2-酮-16α-碳腈(孕烯醇酮16α-碳腈)处理后，细胞色素P-450的丢失不再明显。用3-甲基胆蒽预处理可使动物对去甲肾上腺素的作用产生抵抗。4.小鼠体内给药[100 mg/kg，腹腔注射]能引起肝脏细胞色素P-450的时间依赖性丢失。去甲雄酮也有类似的效果，尽管没有那么明显。所有这三种类固醇都会诱导5-氨基乙酰丙酸合成酶，并在肝脏中积聚卟啉。5.雌性大鼠给药2小时后，肝脏细胞色素P-450的丢失和卟啉类物质的蓄积与雄性相似。6.给予苯巴比妥和去甲肾上腺素或乙炔雌二醇(100 mg/kg，腹腔注射)后，大鼠肝脏内形成绿色色素。这些色素的特征与给予2-烯丙基-2-异丙基乙酰胺后大鼠肝脏中产生的绿色色素相似。对照组和去甲肾上腺素、雌二醇或黄体酮组大鼠的肝脏中均未提取到绿色色素。
1. 19-Nor-17alpha-pregna-1,3,5(10)-trien-20-yne-3,17-diol (ethynyloestradiol) or 17beta-hydroxy-19-nor-17alpha-pregn-4-en-20-yn-3-one (norethindrone) but not 17alpha-ethyl-17beta-hydroxy-19-norandrost-4-en-3-one (norethandrolone) caused a time-dependent loss of cytochrome P-450 when incubated in vitro with rat liver microsomal fractions and NADPH-generating systems. 2. The enzyme system catalysing the norethindrone-mediated loss of cytochrome P-450 had many characteristics of the microsomal mixed-function oxidases. It required NADPH and air, and was inhibited by Co. However, it was unaffected by 1 mM-compound SKF 525A. 3. In microsomal fractions from phenobarbitone-pretreated rats the norethindrone-mediated loss of cytochrome P-450 was increased relative to controls. The norethindrone-mediated cytochrome P-450 loss was less pronounced when the animals were pretreated with 3beta-hydroxy-pregn-5-en-2-one 16alpha-carbonitrile (pregnenolone 16alpha-carbonitrile). Pretreatment with 3-methylcholanthrene rendered the animals resistant to the norethindrone effect. 4. Administration in vivo [100mg/kg, intraperitoneally] of norethindrone or ethinyl oestradiol also produced a time-dependent loss of liver cytochrome P-450. Norethandrolone had a similar, though much less-marked, effect. All three steroids lead to an induction of 5-aminolaevulinate synthase and an accumulation of porphyrins in the liver. 5. The loss of cytochrome P-450 and the accumulation of porphyrins in the liver 2 h after the administration of norethindrone to female rats was similar to that seen in males. 6. Rats pretreated with phenobarbitone and given norethindrone or ethynyloestradiol (100mg/kg, intraperitoneally) formed green pigments in their livers. These had characteristics similar to the green pigments produced in the livers of rats after the administration of 2-allyl-2-isopropylacetamide. No green pigments could be extracted from the livers of control rats or those given norethandrolone, oestradiol or progesterone.