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.