Critical Reviews™ in Eukaryotic Gene Expression

ISSN for PRINT: 1045-4403

For Online Access

Best Paper Award Selection - Editorial Board Site

2002, Volume12

Issue 2

78 pages

DOI: 10.1615/CritRevEukaryotGeneExpr.v12.i2

Issue price - $169.00

Laurie K. McCauley
Department of Periodontics/Prevention/Geriatrics, School of Dentistry, University of Michigan; Department of Pathology, Medical School, University of Michigan

Tolga F. Tozum
Department of Periodontics/Prevention/Geriatrics, School of Dentistry, University of Michigan; Department of Periodontology, Faculty of Dentistry, Hacettepe University, Ankara, Turkey

Thomas J. Rosol
The Ohio State University, Department of Veterinary Biosciences, Columbus, OH 43210

Estrogens have long been known to be important for skeletal homeostasis, but their precise mechanisms of action in bone are still unclear. Mice with targeted deletions of the estrogen receptors a (ERa) and b (ERb) have been generated by two research groups and several studies performed characterizing the phenotype of ERa knockout (ERKOa), ERb knockout (ERKOb), or double deletion of ERa and ERb (DERKO) mice. Initial studies reported a reduction in bone mineral density in male ERKOa mice. More extensive analyses have been puzzling, likely because of compensatory mechanisms in ERKO mice. Furthermore, the existence of a third ER continues to be a potential explanation for some actions of estrogen in bone. Other rodent models, including the testicular feminized mouse and rat, the aromatase knockout mouse, and a rat with a dominant negative ER mutation, have added information regarding estrogen's actions in bone. This review summarizes many reports characterizing available rodent models with genetic alterations relevant to estrogen action. The sum of these reports suggests that the ERb is not highly protective in bone because loss of its function results in minimal alterations in the skeleton. Furthermore, loss of both the ERa and the ERb does not account for loss of estrogen action in bone, because the impact of DERKO is seemingly not as great as the impact of gonadectomy on the skeleton. Finally, through studies of ERKO mice and other rodent models of altered sex steroid action, it appears that estrogen may be more protective in the skeleton than androgens.

DOI: 10.1615/CritRevEukaryotGeneExpr.v12.i2.10 Download article, 12 pages

Article price - $35.00

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