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Bone protection by ...
Bone protection by estrens occurs through non-tissue-selective activation of the androgen receptor.
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- Windahl, Sara H, 1971 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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Galien, René (author)
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Chiusaroli, Riccardo (author)
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Clément-Lacroix, Philippe (author)
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Morvan, Frederic (author)
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Lepescheux, Liên (author)
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Nique, François (author)
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Horne, William C (author)
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Resche-Rigon, Michèle (author)
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Baron, Roland (author)
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(creator_code:org_t)
- 2006
- 2006
- English.
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In: The Journal of clinical investigation. - 0021-9738. ; 116:9, s. 2500-9
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Abstract
Subject headings
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- The use of estrogens and androgens to prevent bone loss is limited by their unwanted side effects, especially in reproductive organs and breast. Selective estrogen receptor modulators (SERMs) partially avoid such unwanted effects, but their efficacy on bone is only moderate compared with that of estradiol or androgens. Estrens have been suggested to not only prevent bone loss but also exert anabolic effects on bone while avoiding unwanted effects on reproductive organs. In this study, we compared the effects of a SERM (PSK3471) and 2 estrens (estren-alpha and estren-beta) on bone and reproductive organs to determine whether estrens are safe and act via the estrogen receptors and/or the androgen receptor (AR). Estrens and PSK3471 prevented gonadectomy-induced bone loss in male and female mice, but none showed true anabolic effects. Unlike SERMs, the estrens induced reproductive organ hypertrophy in both male and female mice and enhanced MCF-7 cell proliferation in vitro. Estrens directly activated transcription in several cell lines, albeit at much higher concentrations than estradiol or the SERM, and acted for the most part through the AR. We conclude that the estrens act mostly through the AR and, in mice, do not fulfill the preclinical efficacy or safety criteria required for the treatment or prevention of osteoporosis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- Animals
- Bone Diseases
- Metabolic
- prevention & control
- Bone and Bones
- drug effects
- physiology
- Breast Neoplasms
- Cell Division
- drug effects
- Cell Line
- Tumor
- Estrenes
- pharmacology
- Estrogen Receptor alpha
- deficiency
- Female
- Humans
- Mice
- Mice
- Inbred C57BL
- Mice
- Knockout
- Orchiectomy
- Ovariectomy
- Receptors
- Androgen
- physiology
- Selective Estrogen Receptor Modulators
- pharmacology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Windahl, Sara H, ...
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Galien, René
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Chiusaroli, Ricc ...
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Clément-Lacroix, ...
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Morvan, Frederic
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Lepescheux, Liên
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show more...
-
Nique, François
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Horne, William C
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Resche-Rigon, Mi ...
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Baron, Roland
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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The Journal of c ...
- By the university
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University of Gothenburg