Cheng D C, Wolfe B M
Atherosclerosis. 1983 Jan;46(1):41-8. doi: 10.1016/0021-9150(83)90162-4.
The progestin, norethindrone acetate has been widely administered to patients in the form of oral contraceptives; however, its hypolipemic action has received little study. This report describes the effects of conventional doses of norethindrone acetate (100 micrograms/day.kg body weight 0.75) on rat plasma lipid levels in vivo as well as the mechanism of action on triglyceride metabolism in isolated hepatocytes in vitro. Norethindrone acetate administration led to significant and proportional reductions of the concentrations of triglycerides, cholesterol and phospholipids of plasma lipoproteins of density less than 1.006 of rats fed a high carbohydrate diet. Norethindrone acetate (0.1 mM) also significantly inhibited the incorporation of both [9,10(-3)H] palmitate and [U-14C]glycerol into triglycerides of isolated hepatocytes from fed rats, by 11 to 16% (P less than 0.001). Release of labeled triglycerides from the isolated hepatocytes was similarly inhibited, 21% and 46%, respectively (P less than 0.05). At the higher concentration of 1.0 mM, norethindrone acetate inhibited the incorporation of [2(-3)H]glycerol into hepatocytic triglycerides by 35-39% (P less than 0.05). The present findings suggest that inhibition of hepatic triglyceride synthesis can account for the reduction of hepatic triglyceride secretion and for at least part of the lowering of plasma VLDL levels which occurs during administration of norethindrone acetate in the rat.
孕激素醋酸炔诺酮已作为口服避孕药被广泛应用于患者；然而，其降血脂作用鲜少得到研究。本报告描述了常规剂量的醋酸炔诺酮（100微克/天·千克体重0.75）对大鼠体内血浆脂质水平的影响以及对体外分离的肝细胞中甘油三酯代谢的作用机制。给喂食高碳水化合物饮食的大鼠服用醋酸炔诺酮导致其血浆脂蛋白密度小于1.006的甘油三酯、胆固醇和磷脂浓度显著且成比例地降低。醋酸炔诺酮（0.1毫摩尔）还显著抑制了来自喂食大鼠的分离肝细胞中[9,10(-3)H]棕榈酸酯和[U-14C]甘油掺入甘油三酯，抑制率为11%至16%（P<0.001）。从分离的肝细胞中释放标记的甘油三酯同样受到抑制，分别为21%和46%（P<0.05）。在1.0毫摩尔的较高浓度下，醋酸炔诺酮抑制[2(-3)H]甘油掺入肝细胞甘油三酯35 - 39%（P<0.05）。目前的研究结果表明，抑制肝脏甘油三酯合成可解释肝脏甘油三酯分泌的减少以及大鼠服用醋酸炔诺酮期间血浆极低密度脂蛋白水平降低的至少部分原因。
