Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in mouse uterine epithelial cells.
The regulation of 3-hydroxy-3-methylglutaryl-CoA reductase was studied in mouse uterine epithelium. The enzyme was rapidly inactivated during incubation with ATP/Mg2+ in vitro, and could be re-activated by incubation with partially purified rat liver phosphoprotein phosphatase. Enzyme activity was rapidly inhibited by mevalonate injection in vivo to approx. 30% of control. The percentage of total enzyme active in vivo was measured by inclusion of NaF in the isolation buffers. The percentage of enzyme active in vivo 18 h after stimulation by oestrogens remained at approx. 25% after inhibition of activity by mevalonate injection, cholesterol feeding or progesterone pretreatment. However, 9 h after oestrogen stimulation, cholesterol feeding inhibited enzyme activity to 57% of control, 94% of which was in the active form. We conclude that, although all components for a reversible phosphorylative regulation of 3-hydroxy-3-methylglutaryl-CoA reductase activity are present in uterine epithelial cells, a role in the rapid changes in epithelial enzyme activity has not been demonstrated.
D000818:Animals; D002784:Cholesterol / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology; D005260:Female; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008798:Mevalonic Acid / Q000494:pharmacology; D051379:Mice; D010749:Phosphoprotein Phosphatases / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D011494:Protein Kinases / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects / Q000201:enzymology*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011374:Progesterone; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases; D008798:Mevalonic Acid