炔诺酮或炔雌醇导致大鼠肝脏细胞色素P - 450减少。

Decreased liver cytochrome P-450 in rats caused by norethindrone or ethynyloestradiol.

作者信息

White I N, Muller-Eberhard U

出版信息

Biochem J. 1977 Jul 15;166(1):57-64. doi: 10.1042/bj1660057.

DOI:10.1042/bj1660057

PMID:901418

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1164956/

Abstract

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.

摘要

19-去甲-17α-孕甾-1,3,5(10)-三烯-20-炔-3,17-二醇（炔雌醇）或17β-羟基-19-去甲-17α-孕-4-烯-20-炔-3-酮（炔诺酮），但不是17α-乙基-17β-羟基-19-去甲雄甾-4-烯-3-酮（诺乙雄龙），在体外与大鼠肝脏微粒体组分和NADPH生成系统一起孵育时，会导致细胞色素P-450随时间减少。2. 催化炔诺酮介导的细胞色素P-450减少的酶系统具有微粒体混合功能氧化酶的许多特性。它需要NADPH和氧气，并受到一氧化碳的抑制。然而，它不受1 mM化合物SKF 525A的影响。3. 在苯巴比妥预处理大鼠的微粒体组分中，炔诺酮介导的细胞色素P-450减少相对于对照组有所增加。当动物用3β-羟基-孕-5-烯-2-酮16α-腈（孕烯醇酮16α-腈）预处理时，炔诺酮介导的细胞色素P-450减少不太明显。用3-甲基胆蒽预处理使动物对炔诺酮的作用产生抗性。4. 体内给予[100mg/kg，腹腔注射]炔诺酮或炔雌醇也会导致肝脏细胞色素P-450随时间减少。诺乙雄龙有类似的作用，尽管不太明显。所有三种甾体都会导致肝脏中5-氨基乙酰丙酸合酶的诱导和卟啉的积累。5. 给雌性大鼠注射炔诺酮2小时后，肝脏中细胞色素P-450的减少和卟啉的积累与雄性大鼠相似。6. 用苯巴比妥预处理并给予炔诺酮或炔雌醇（100mg/kg，腹腔注射）的大鼠肝脏中形成绿色色素。这些色素的特性与给予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。从对照大鼠或给予诺乙雄龙、雌二醇或孕酮的大鼠肝脏中无法提取到绿色色素。