Developmental regulation of the expression of genes encoding proteins involved in cholesterol homeostasis.
The developmental patterns of expression of HMG-CoA reductase, farnesyl pyrophosphate synthase, cholesterol 7 alpha-hydroxylase, and LDL receptor were investigated using Northern blotting analysis to quantitate mRNA levels. It was found that HMG-CoA reductase and farnesyl pyrophosphate synthase mRNA levels in brain reached peaks at age 4 days which correlates with the time of peak enzyme activity and the onset of rapid brain growth and myelination. In liver, HMG-CoA reductase and cholesterol 7 alpha-hydroxylase mRNA both rose dramatically at weaning. This is consistent with the concept that de novo synthesized cholesterol is the preferred substrate for cholesterol 7 alpha-hydroxylase and may also be involved in the induction of the enzyme. In testes, HMG-CoA reductase activity was highest at age 21 days and then declined, while LDL receptor mRNA levels rose from age 31 to 120 days. These studies suggest a major role for de novo cholesterol synthesis in developing brain, liver, and testes.
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Department of Biochemistry and Molecular Biology, College of Medicine, University of South Florida, Tampa 33612.
D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis; D015152:Blotting, Northern; D001921:Brain / Q000201:enzymology*; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000096:biosynthesis; D004122:Dimethylallyltranstransferase / Q000096:biosynthesis; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis; D008099:Liver / Q000201:enzymology; D008297:Male; D009186:Myelin Sheath / Q000502:physiology; D010088:Oxidoreductases / Q000096:biosynthesis*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000096:biosynthesis*; D013091:Spermatogenesis; D013379:Substrate Specificity; D013737:Testis / Q000201:enzymology
D001647:Bile Acids and Salts; D012333:RNA, Messenger; D011973:Receptors, LDL; D002784:Cholesterol; D010088:Oxidoreductases; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase; D004122:Dimethylallyltranstransferase