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This Article Full Text Full Text (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. K PubMed PubMed Citation Articles by Engdahl, C. Articles by Lagerquist, M. K

Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Guldhedsgatan 10A, 413 46 Gothenburg, Sweden
¹ Department of Biosciences and Nutrition at NOVUM, Karolinska Institute, Huddinge 17177, Sweden
² Hubrecht Institute, Utrecht 3508 AD, The Netherlands

(Correspondence should be addressed to C Engdahl; Email: cecilia.engdahl{at}rheuma.gu.se)

Raloxifene is a selective oestrogen receptor modulator with tissue-specific effects. The mechanisms behind the effects of raloxifene are partly unclear, and the aim of the present study was to investigate whether raloxifene can activate the classical oestrogen-signalling pathway in vivo in three known oestrogen-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 oestrogen-responsive elements (EREs), enabling detection of in vivo activation of gene transcription via the classical oestrogen pathway. Three-month-old ovariectomized ERE-luciferase mice were treated with the raloxifene analogue (LY117018), oestradiol (OE₂) or vehicle for 3 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 (BMD) to the same extent as OE₂, and both treatments resulted in increased luciferase activity in bone. As expected, OE₂ 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 OE₂. LY117018 and OE₂ treatment resulted in similar luciferase activation in thymus. However, only OE₂ 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 oestrogen pathway in bone, uterus and thymus in vivo, and this activation is associated with BMD and uterus weight, but not thymus weight.