Regulation of HMG-CoA Reductase Gene Expression in the Corpus Luteum: Role of Estradiol
HMG-CoA reductase, the rate limiting enzyme in cholesterol biosynthesis, is regulated in both steroidogenic and nonstcroidogenic cells via negative feedback mechanism by either sterols or their metabolites. Steroidogenic tissues have, in addition, another mode of enzyme regulation due to their marked need for cholesterol substrate. We have previously demonstrated that estradiol enhances markedly and specifically the activity of this enzyme in the corpus luteum of the pregnant rat. The observation that estradiol stimulates hMG-CoA reductase activity without changing the phosphorylation/dephosphorylation state of the enzyme led us to hypothesize that estradiol acts to specifically increase hMG-Co A reductase synthesis by increasing mRNAlevels encoding this protein. This hypothesis has been directly tested using a cDNA and an antibody for hMG-CoA reductase message and protein, respectively. In addition, since a decrease in cellular sterol upregulates the level of hMG-Co A reductase mRNA, we examined the possibility that estradiol’s action on hMG-Co A reductase activity, content and mRNA is mediated by estradiol depletion of cholesterol storage.
KeywordsCorpus Luteum Luteal Cell Estradiol Treatment Reductase mRNA Cholesterol Storage
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