In vivo activation of gene transcription via oestrogen response elements by a raloxifene analogue
| Autor: | Marie K Lagerquist, Hans Carlsten, Paul T. van der Saag, Cecilia Engdahl, Jan-Ake Gustafsson, Caroline Jochems |
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| Přispěvatelé: | Hubrecht Institute for Developmental Biology and Stem Cell Research |
| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Pyrrolidines Transcription Genetic medicine.drug_class Endocrinology Diabetes and Metabolism Uterus Estrogen receptor Mice Transgenic Thiophenes Thymus Gland Biology Response Elements Mice Endocrinology Bone Density In vivo Internal medicine medicine Animals Luciferase Raloxifene Femur Luciferases Estradiol Estrogen Antagonists Estrogens Organ Size medicine.anatomical_structure Receptors Estrogen Selective estrogen receptor modulator Estrogen Raloxifene Hydrochloride Mice Inbred CBA Ovariectomized rat Female medicine.drug |
| Zdroj: | Journal of Endocrinology, 203(3), 349-356. Society for Endocrinology |
| ISSN: | 1479-6805 0022-0795 |
| DOI: | 10.1677/joe-09-0012 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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