Weinstein I, Soler-Argilaga C, Werner H V, Heimberg M
Biochem J. 1979 May 15;180(2):265-71. doi: 10.1042/bj1800265.
Normal female rats were given 15mug of ethynyloestradiol/kg body wt. for 14 days and were killed on day 15 after starvation for 12-14h. The livers were isolated and were perfused with a medium containing washed bovine erythrocytes, bovine serum albumin, glucose and [1-(14)C]oleic acid; 414mumol of oleate were infused/h during a 3h experimental period. The output of bile and the flow of perfusate/g of liver were decreased in livers from animals pretreated with ethynyloestradiol, whereas the liver weight was increased slightly. The rates of uptake and of utilization of [1-(14)C]oleate were measured when the concentration of unesterified fatty acid in the perfusate plasma was constant. The uptake of unesterified fatty acid was unaffected by pretreatment of the animal with oestrogen; however, the rate of incorporation of [1-(14)C]oleate into hepatic and perfusate triacylglycerol was stimulated, whereas the rate of conversion into ketone bodies was impaired by treatment of the rat with ethynyloestradiol. Pretreatment of the rat with ethynyloestradiol increased the output of very-low-density lipoprotein triacylglycerol, cholesterol, phospholipid and protein. The production of (14)CO(2) and the incorporation of radioactivity into phospholipid, cholesteryl ester and diacylglycerol was unaffected by treatment with the steroid. The net output of glucose by livers from oestrogen-treated rats was impaired despite the apparent increased quantities of glycogen in the liver. The overall effect of pretreatment with oestrogen on hepatic metabolism of fatty acids is the channeling of [1-(14)C]oleate into synthesis and increased output of triacylglycerol as a moiety of the very-low-density lipoprotein, whereas ketogenesis is decreased. The effect of ethynyloestradiol on the liver is apparently independent of the nutritional state of the animal from which the liver was obtained. It is pertinent that hepatocytes prepared from livers of fed rats that had been treated with ethynyloestradiol produced fewer ketone bodies and secreted more triacylglycerol than did hepatocytes prepared from control animals. In these respects, the effects of the steroid were similar in livers from fed or starved (12-14h) rats. Oestrogens may possibly inhibit hepatic oxidation of fatty acid, making more fatty acid available for the synthesis of triacylglycerol, or may stimulate the biosynthesis of triacylglycerol, or may be active on both metabolic pathways.
给正常雌性大鼠按每千克体重15微克的剂量注射乙炔雌二醇，持续14天，并在饥饿12 - 14小时后的第15天处死。分离肝脏，并用含有洗涤过的牛红细胞、牛血清白蛋白、葡萄糖和[1 - (14)C]油酸的培养基进行灌注；在3小时的实验期间，每小时注入414微摩尔油酸。与未用乙炔雌二醇预处理的动物的肝脏相比，用乙炔雌二醇预处理的动物的肝脏胆汁分泌量和每克肝脏的灌注液流量降低，而肝脏重量略有增加。当灌注液血浆中未酯化脂肪酸的浓度恒定时，测量[1 - (14)C]油酸的摄取和利用速率。未酯化脂肪酸的摄取不受雌激素对动物预处理的影响；然而，[1 - (14)C]油酸掺入肝脏和灌注液三酰甘油的速率受到刺激，而乙炔雌二醇处理大鼠后，其转化为酮体的速率受损。用乙炔雌二醇预处理大鼠会增加极低密度脂蛋白三酰甘油、胆固醇、磷脂和蛋白质的输出。(14)CO(2)的产生以及放射性掺入磷脂、胆固醇酯和二酰甘油不受该类固醇处理的影响。尽管肝脏中糖原含量明显增加，但用雌激素处理的大鼠的肝脏葡萄糖净输出受损。雌激素预处理对肝脏脂肪酸代谢的总体影响是将[1 - (14)C]油酸导向合成并增加作为极低密度脂蛋白一部分的三酰甘油的输出，而酮体生成减少。乙炔雌二醇对肝脏的影响显然与获取肝脏的动物的营养状态无关。值得注意的是，用乙炔雌二醇处理的喂食大鼠的肝脏制备的肝细胞比对照动物制备的肝细胞产生的酮体更少，分泌的三酰甘油更多。在这些方面，该类固醇在喂食或饥饿（12 - 14小时）大鼠的肝脏中的作用相似。雌激素可能抑制肝脏脂肪酸氧化，使更多脂肪酸可用于三酰甘油合成，或者可能刺激三酰甘油的生物合成，或者可能对这两种代谢途径都有作用。
