Estrogen receptor specificity in the regulation of the skeleton in female mice.

• There are two known estrogen receptors, estrogen receptor-alpha (ER alpha) and estrogen receptor-beta (ER beta), which may mediate the actions of estrogen. The aim of the present study was to compare fat content, skeletal growth and adult bone metabolism in female mice lacking ER alpha (ERKO), ER beta (BERKO) or both ERs (DERKO). We demonstrate that endogenous estrogens decrease the fat content in female mice via ER alpha and not ER beta. Interestingly, the longitudinal bone growth was decreased in ERKO, increased in BERKO, but was intermediate in DERKO females, demonstrating that ER alpha and ER beta exert opposing effects in the regulation of longitudinal bone growth. The effects on longitudinal bone growth were correlated with similar effects on serum levels of IGF-I. A complex regulation of the trabecular bone mineral density (BMD), probably caused by a disturbed feedback regulation of estrogen and testosterone, was observed in female ER-inactivated mice. Nevertheless, a partial functional redundancy for ER alpha and ER beta in the maintenance of the trabecular BMD was observed in the female mice at 60 days of age. Thus, ER alpha and ER beta may have separate effects (regulation of fat), opposing effects (longitudinal bone growth) or partial redundant effects (trabecular BMD at 60 days of age), depending on which parameter is studied.

Keyword

Absorptiometry

Photon

methods

Animals

Body Constitution

Bone Density

physiology

Estrogen Receptor alpha

Estrogen Receptor beta

Female

Femur

growth & development

metabolism

radiography

Insulin-Like Growth Factor I

metabolism

Linear Models

Mice

Mice

Inbred C57BL

Mice

Knockout

Receptors

Estrogen

genetics

metabolism

Tomography

X-Ray Computed

Publication and Content Type

ref (subject category)

art (subject category)