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The effect of 17{beta}-estradiol on cholesterol content in human macrophages is influenced by the lipoprotein milieu.
MedLine Citation:
PMID:  21646386     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Estrogen and testosterone are thought to modulate coronary heart disease (CHD) risk. To examine how these hormones affect human macrophage cholesterol transport, a key factor in atherogenesis, we obtained monocytes from healthy male and postmenopausal female donors (age 50-70 y). Cells were allowed to differentiate in autologous serum. Human monocyte-derived macrophages (HMDMs) were exposed to estrogen, testosterone, or vehicle, during differentiation. Cells were cholesterol-enriched with oxidized LDL (oxLDL) in the presence of treatment. Cell cholesterol mass, efflux, and the expression of proteins involved in HMDM cholesterol transport were examined. Estrogen significantly reduced cholesteryl ester content in both female and male HMDMs while having no measurable effect on cholesterol efflux. Testosterone did not affect cholesterol content or efflux. Both hormones significantly but modestly affected the gene expression of several proteins involved in HMDM transport, yet these effects did not translate into significant changes in protein expression. In THP-1 macrophages, the effect of estrogen on cholesteryl ester content was more potent in unloaded macrophages and was estrogen receptor-dependent. A trend for a reduction in non-oxidized LDL uptake by estrogen was observed and was also found to be dependent upon ER activation. Our data indicate that estrogen, but not testosterone, reduces cholesteryl ester accumulation in HMDMs obtained from a CHD-age relevant population, independent of changes in the expression of proteins important to macrophage cholesterol transport. In THP-1 cells, this effect is reduced in the presence of oxLDL indicating that a pro-atherogenic lipoprotein milieu is an important variable in sex hormone modulation of CHD.
Authors:
Michael P Corcoran; Alice H Lichtenstein; Mohsen Meydani; Alice Dillard; Ernst J Schaefer; Stefania Lamon-Fava
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-6
Journal Detail:
Title:  Journal of molecular endocrinology     Volume:  -     ISSN:  1479-6813     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-6-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8902617     Medline TA:  J Mol Endocrinol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
M Corcoran, Tufts University, Boston, 02111, United States.
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