Regulation by plasma lipoproteins of progesterone biosynthesis and 3-hydroxy-3-methyl glutaryl coenzyme a reductase activity in cultured human choriocarcinoma cells.
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.
D002478:Cells, Cultured; D002822:Choriocarcinoma / Q000378:metabolism*; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood* / Q000494:pharmacology; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011284:Pregnenolone / Q000096:biosynthesis; D011374:Progesterone / Q000096:biosynthesis*; D014594:Uterine Neoplasms / Q000378:metabolism*
D008074:Lipoproteins; D011374:Progesterone; D011284:Pregnenolone; D006903:Hydroxymethylglutaryl CoA Reductases