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Estrogen receptor specificity for the effects of estrogen in ovariectomized mice
M K Lindberg1, Z Weihua, N Andersson
1Division of Endocrinology, Department of Internal Medicine, Gröna Stråket 8, Sahlgrenska University Hospital, S-41345 Göteborg, Sweden.
Abstract:
Estrogen exerts a variety of important physiological effects, which have been suggested to be mediated via the two known estrogen receptors (ERs), alpha and beta. Three-month-old ovariectomized mice, lacking one or both of the two estrogen receptors, were given estrogen subcutaneously (2.3 micro g/mouse per day) and the effects on different estrogen-responsive parameters, including skeletal effects, were studied. We found that estrogen increased the cortical bone dimensions in both wild-type (WT) and double ER knockout (DERKO) mice. DNA microarray analysis was performed to characterize this effect on cortical bone and it identified four genes that were regulated by estrogen in both WT and DERKO mice. The effect of estrogen on cortical bone in DERKO mice might either be due to remaining ERalpha activity or represent an ERalpha/ERbeta-independent effect. Other effects of estrogen, such as increased trabecular bone mineral density, thymic atrophy, fat reduction and increased uterine weight, were mainly ERalpha mediated.
Insights
Estrogen impacts bone dimensions through estrogen receptors (ERs). Some effects on cortical bone may not require ERalpha or ERbeta, suggesting independent pathways for estrogen signaling.
Area of Science:
- Endocrinology
- Skeletal Biology
- Molecular Biology
Background:
- Estrogen mediates physiological effects through estrogen receptors (ERs), primarily ERalpha and ERbeta.
- Understanding the specific roles of each ER in mediating estrogen's diverse actions is crucial.
Purpose of the Study:
- To investigate the roles of ERalpha and ERbeta in mediating estrogen's effects on skeletal and other physiological parameters.
- To identify estrogen-responsive genes in cortical bone.
Main Methods:
- Ovariectomized mice lacking ERalpha, ERbeta, or both were treated with estrogen.
- Cortical bone dimensions, trabecular bone mineral density, thymic atrophy, fat reduction, and uterine weight were assessed.
- DNA microarray analysis was used to characterize gene expression changes in cortical bone.
Main Results:
- Estrogen increased cortical bone dimensions in wild-type and double ER knockout mice.
- Four genes were identified as estrogen-regulated in cortical bone of both genotypes.
- Estrogen's effects on trabecular bone, thymus, fat, and uterus were predominantly mediated by ERalpha.
Conclusions:
- Estrogen's effects on cortical bone dimensions may involve ERalpha-independent pathways.
- ERalpha is the primary mediator of estrogen's effects on trabecular bone, thymus, fat, and uterus.