Development of osteoporosis and obesity in ovariectomized estrogen receptor β knock out and wild type mice.

Bước tới: chuyển hướng, tìm kiếm

Tác giả: D.Seidlová-Wuttke1, T. Vortherms1, N.B. Tiep1, J.A. Gustafsson2, W. Wuttke1.

(1) Dept. of Endocrinology University of Goettingen, Germany ; (2) Dept. of Medical Nutrition and Dept. of Bioscience Karolinska Institute, Huddinge, Sweden.

The 4th Meetting of CASCADE - Chemicals as Contaminants in the food chain (Network of Excellence for Research, Risk Assessment and Education) - Brussels, Belgium, May 2008.

Estrogen receptor β knock out (BERKO) mice have been amply used to study the function of the estrogen receptor of the beta subtype (ERβ). A relatively inconspicuous body weight and bone phenotype as well as little effects of short term ovariectomy (ovx) has been reported. Long lasting studies on the bone phenotype of intact and ovx mice are lacking. Utilizing quantitative computer tomography (qCT) we therefore determined mineral densities of the cancellous and cortical bone of the metaphysis of the tibia as well as their respective sizes, in intact and ovx BERKO mice and compared the data with those determined in wild type (WT) animals. In addition, the development of body weights (BW) of a paratibially located, estrogen regulated fat depot was studied. Animals were ovx at 3 months of age and qCT analysis performed in 2-4 months intervals until 12 months of age, i.e. until 9 months after ovx. There were few significant differences in development of BW, size of fat depots, trabecular and cortical desities as well as of their areas observed in the intact BERKO animals as compared to the intact WT mice. Following ovx, however, marked differences were unmarked. OVX WT animals gained BW and had increased size of the fat depot within 2 months after ovx while such obesity developed much later in the ovx BERKO mice. At months 7 and 9 after ovx, BERKO mice were significantly heavier than the respective WT mice. Similar differences in development of osteoporosis could be demonstrated, i.e. ovx WT animals lost trabecular density more rapidly than the BERKO mice which caught up however, 7 months after ovx and later. Similar effects could be determined for the cortical parameters.

It is concluded that the absence of ERβ in ovx BERKO animals during the first 3-5 months following ovx had protective effects against obesity and osteoporosis which, however, vanished at later time points. The molecular mechanisms of this late "normalization" of ovx induced effects in BERKO remain to be determined.

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