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 estr ogen. The aim of the present study was to compare fat content, skeletal gro wth and adult bone metabolism in female mice lacking ER alpha, (EPKO), ER b eta (BERKO) or both ERs (DERKO). We demonstrate that endogenous estrogens d ecrease the fit content in female mice via ER alpha and not ER beta. Intere stingly, the longitudinal bone growth was decreased in ERKO, increased in B ERKO, but,vas intermediate in DERKO females, demonstrating that ER alpha an d ER beta exert opposing effects in the regulation of longitudinal bone gro wth. The effects on longitudinal bone growth were correlated with similar e ffects on serum levels of IGF-I. A complex regulation of the trabecular bon e 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 (regulat ion of fat), opposing effects (longitudinal bone growth) or partial redunda nt effects (trabecular BMD at 60 days of age), depending on which parameter is studied.