17-β-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 24 It period. The data indicate that the transcript levels of interleukin 1 receptor antagonist (IL-1ra), beta 2-microglobulin, annexin XI and the LXRalpha 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 LXRalpha and IL-1ra through dissimilar pathways. (C) 2002 Elsevier Science Ltd. All rights reserved.