17-Beta-estradiol regulates expression of genes that function in macrophage activation and cholesterol homeostasis.
Macrophage activation and cholesterol processing can be affected by changes in estrogen concentrations. However, there is a paucity of information about the genes and mechanisms regulating this estrogen effect. In primary monocyte-derived macrophages we detected transcript and protein for estrogen receptor beta (ERbeta). Determination of genes regulated by estrogen was completed using cDNA arrays and semiquantitative RT-PCR on RNA isolated from macrophages cultured in serum free media containing (5-10) x 10(-9)M 17-beta-estradiol and subsequently deprived of estrogen for a 24h period. The data indicate that the transcript levels of interleukin 1 receptor antagonist (IL-1ra), beta 2-microglobulin, annexin XI and the LXR(alpha) receptor significantly increased and that Ly-GDI transcript levels significantly decreased after estrogen withdrawal; data congruent with estrogen depletion regulating macrophage inflammatory and biochemical processes. Treatment of THP-1 cells with phorbol 12-myristate-13-acetate in the presence or absence of estrogen indicate that differentiation to a macrophage-like cell type was a prerequisite for production of the estrogen response. In addition, experiments using cycloheximide treatment, that blocks nascent protein synthesis, indicated that estrogen withdrawal affected the transcript levels of LXR(alpha) and IL-1ra through dissimilar pathways.
Kramer
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PR
Department of Biomedical Sciences, Baylor College of Dentistry, Texas A&M University Health Science Center, 3302 Gaston Avenue, Dallas, TX, USA. pkramer@tambcd.edu
Wray
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D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism / Q000502:physiology*; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism; D013997:Time Factors
D018076:DNA, Complementary; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013629:Tamoxifen; D004958:Estradiol; D012313:RNA; D002784:Cholesterol; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate