Simpson E R, Porter J C, Milewich L, Bilheimer D W, MacDonald P C
J Clin Endocrinol Metab. 1978 Nov;47(5):1099-105. doi: 10.1210/jcem-47-5-1099.
The regulation of both the activity of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase [mevalonate-NADP+ oxidoreductase (CoA-acylating) EC 1.1.1.34] and the secretion of progesterone by human plasma lipoproteins has been investigated in human choriocarcinoma cells in culture. HMG CoA reductase activity was computed from the rate of formation of [14C]mevalonolactone from [14C]HMG CoA. The activity of HMG CoA reductase was expressed as nanomoles of mevalonolactone formed/min . mg solubilized cell protein. An inverse relationship was found between the presence of lipoprotein in the culture medium and the activity of HMG CoA reductase in these cells. In cells maintained in the presence of lipoprotein-enriched culture medium containing 840 micrograms cholesterol/ml, the average activity of HMG CoA reductase was 0.25 nmol/min . mg protein. After removal of lipoprotein, the activity of HMG CoA reductase increased to 1.3 nmol/min . mg protein. The average activity of HMG CoA reductase in cells maintained in lipoprotein-deficient culture medium was 1.5 nmol/min . mg protein but fell to 0.3 nmol/min . mg protein after addition of lipoprotein to the medium. When cells were maintained in the presence of lipoprotein, the rates of section of progesterone and pregnenolone into the culture medium were 2-8 times greater than the rates of secretion of these steroids by cells maintained in the absence of lipoprotein. On the basis of these results, it is concluded that lipoproteins control the rate of cholesterol biosynthesis in cultured choriocarcinoma cells by regulating the activity of HMG CoA reductase, and control the rate of synthesis of progesterone by providing the precursor, cholesterol. We suggest that progesterone synthesis by the trophoblast of the human placenta may also be regulated by the uptake of lipoprotein from maternal blood.
在培养的人绒毛膜癌细胞中，对3-羟基-3-甲基戊二酰辅酶A（HMG CoA）还原酶[甲羟戊酸-NADP +氧化还原酶（辅酶A酰化），EC 1.1.1.34]的活性以及人血浆脂蛋白对孕酮分泌的调节进行了研究。HMG CoA还原酶活性是根据[14C] HMG CoA生成[14C]甲羟戊酸内酯的速率计算得出的。HMG CoA还原酶的活性以每分钟形成的甲羟戊酸内酯的纳摩尔数表示/毫克可溶解的细胞蛋白。在培养基中脂蛋白的存在与这些细胞中HMG CoA还原酶的活性之间发现了反比关系。在含有840微克胆固醇/毫升的富含脂蛋白的培养基中培养的细胞中，HMG CoA还原酶的平均活性为0.25纳摩尔/分钟·毫克蛋白质。去除脂蛋白后，HMG CoA还原酶的活性增加到1.3纳摩尔/分钟·毫克蛋白质。在缺乏脂蛋白的培养基中培养的细胞中，HMG CoA还原酶的平均活性为1.5纳摩尔/分钟·毫克蛋白质，但在向培养基中添加脂蛋白后降至0.3纳摩尔/分钟·毫克蛋白质。当细胞在脂蛋白存在下培养时，孕酮和孕烯醇酮分泌到培养基中的速率比在无脂蛋白条件下培养的细胞分泌这些类固醇的速率高2-8倍。基于这些结果，可以得出结论，脂蛋白通过调节HMG CoA还原酶的活性来控制培养的绒毛膜癌细胞中胆固醇的生物合成速率，并通过提供前体胆固醇来控制孕酮的合成速率。我们认为，人胎盘滋养层细胞的孕酮合成也可能受到母体血液中脂蛋白摄取的调节。
