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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-09-0012v1 203/3/349    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Engdahl, C. Articles by Lagerquist, M. PubMed PubMed Citation Articles by Engdahl, C. Articles by Lagerquist, M.

C Engdahl, Rheumatology and Inflammation Research, Inst. of Medicine, Sahlgrenska Academy at University of Gothenburg, Göteborg, SE-413 46, Sweden
C Jochems, Dept. of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Inst. of Medicine, Gothenburg, Sweden
J Gustafsson, Dept. of Biosciences and Nutrition at NOVUM, Karolinska Institute, Huddinge, Sweden, Stockholm, Sweden
P van der Saag, Hubrecht Inst, Utrecht, The Netherlands, Utrecht, Netherlands
H Carlsten, Dept. of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Inst. of Medicine, Gothenburg, Sweden
M Lagerquist, Dept. of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Inst. of Medicine, Gothenburg, Sweden

Correspondence: Cecilia Engdahl, Email: cecilia.engdahl{at}rheuma.gu.se

Raloxifene is a selective estrogen receptor modulator (SERM) with tissue-specific effects. The mechanisms behind the effects of raloxifene are partly unclear and the aim of the present study was to investigate if raloxifene can activate the classical estrogen signalling pathway in vivo in three known estrogen-responsive organs, uterus (reproductive organ), bone (non-reproductive organ) and thymus (immune organ). For this purpose we have used reporter mice with a luciferase gene under control of estrogen responsive elements (EREs), enabling detection of in vivo activation of gene transcription via the classical estrogen pathway.

Three-month-old ovariectomized ERE-luciferase mice were treated with the raloxifene analogue (LY117018), estradiol or vehicle for three weeks. Luciferase activation was measured in bone, uterus and thymus, and compared to bone parameters, and uterus and thymus weights.

The raloxifene analogue affected bone mineral density to the same extent as estradiol, and both treatments resulted in increased luciferase activity in bone. As expected, estradiol treatment resulted in increased uterus weight and increased uterine luciferase activity, while the effect of LY117018 on uterus weight and luciferase activity was modest and significantly lower than the effect of estradiol. LY117018 and estradiol treatment resulted in similar luciferase activation in thymus. However, only estradiol treatment resulted in thymic atrophy while no effect on thymus weight was seen after LY117018 treatment. In summary, the raloxifene analogue LY117018 can activate the classical estrogen pathway in bone, uterus and thymus in vivo, and this activation is associated with bone mineral density and uterus weight, but not thymus weight.