The balance between ER-alpha and ER-beta in fibroblasts may be crucial in the physiological response to ligands. Up- or down-regulation of the ERs in response to different compounds could mediate the reversal of certain age-related changes in skin and connective tissue. The time-dependent effects of 17-beta estradiol, raloxifene and tamoxifen on ER-alpha and ER-beta mRNA expression in the skin fibroblast cultures were performed. Experiments were carried out in primary cultures of human skin fibroblasts obtained from postmenopausal women. The cells were cultured in medium containing: 2 micromol/l estradiol (E2), 4 micromol/l tamoxifen (Tx) or 4 micromol/l raloxifene (Rx) for 7, 24 and 32 h. ER-alpha and ER-beta mRNAs were measured by quantitative assays based on reverse transcription (RT) of the mRNA and polymerase chain reaction (PCR) amplification of the cDNA. We suggest that ER-alpha and ER-beta are co-expressed in human postmenopausal skin fibroblast and documented that the level of mRNA expression of ERs in this tissue is estradiol, raloxifene or tamoxifen regulated as a mechanism to control the action of those ligands on the cell. On the basis of ER mRNA expression levels, fibroblast response to estradiol appears to be modulated by up-regulation of ER-beta rather than ER-alpha. Two of the examined SERMs appear to have different response to modulation of ERs: response of raloxifen is modulated by up-regulation of ER-beta, and no changes in expression of ER-alpha and tamoxifen response seem to be modulated by ER down-regulation in short-term or up-regulation during longer treatment.
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