We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Estrogen Reduces Lipid Content in the Liver Exclusively from Membrane Receptor Signaling.
- Authors
Pedram, Ali; Razandi, Mahnaz; O'Mahony, Fiona; Harvey, Harry; Harvey, Brian J.; Levin, Ellis R.
- Abstract
Estrogen induces signal transduction through estrogen receptor α (ERα), which localizes to both the plasma membrane and nucleus. Using wild-type mice, ERα knockout (ERKO) mice, or transgenic mice expressing only the ligand-binding domain of ERα exclusively at the plasma membrane (MOER), we compared the transcriptional profiles of liver tissue extracts after mice were injected with the ERα agonist propyl-pyrazole-triol (PPT). The expression of many lipid synthesis-related genes was comparably decreased in livers from MOER or wild-type mice but was not suppressed in ERKO mice, indicating that only membrane-localized ERα was necessary for their suppression. Cholesterol, triglyceride, and fatty acid content was decreased only in livers from wild-type and MOER mice exposed to PPT, but not in the livers from the ERKO mice, validating the membrane-driven signaling pathway on a physiological level. PPT-triggered activation of ERα at the membrane induced adenosine monophosphate-activated protein kinase to phosphorylate sterol regulatory element-binding factor 1 (Srebf1), preventing its association with and therefore its proteolytic cleavage by site-1 protease. Consequently, Srebf1 was sequestered in the cytoplasm, preventing the expression of cholesterol synthesis-associated genes. Thus, we showed that inhibition of gene expression mediated by membrane-localized ERα caused a metabolic phenotype that did not require nuclear ERα.
- Publication
Science Signaling, 2013, Vol 6, Issue 276, p1
- ISSN
1945-0877
- Publication type
Article
- DOI
10.1126/scisignal.2004013