Effect of tamoxifen treatment on body temperature and bone regulation in mice

As a selective estrogen receptor modulator, tamoxifen is known to act as estrogen receptor (ER) antagonist in ER positive cancer cells. Since many of the metabolic functions of estrogen are mediated by ER⍺ in the hypothalamus, we hypothesized that tamoxifen affects body temperature and bone metabolism by modulating ER⍺ signaling in the hypothalamus. To test this hypothesis, a genetic mice model that lacks ER⍺ in the medial basal hypothalamus were used. These ER⍺ knock-out mice and wild-type littermates were treated with either tamoxifen or vehicle for four weeks. Their body weight, core body temperature, tail skin temperature femoral bone length and density were measured. Tamoxifen treatment reduced core body temperature in wild-type but not ER⍺ brain knock-out mice. On the other hand, tamoxifen increased bone mass in wild-type while it reduced bone mass when ER⍺ is knocked out in the hypothalamus. These data indicate that tamoxifen could affect body temperature via ER⍺ in the hypothalamus and bone density in different ways in the periphery versus the brain