2-Methoxyestradiol inhibits longitudinal bone growth in normal female rats

2-Methoxyestradiol (2-MeO-E-2), a major metabolite of 17 beta-estradiol, ma y function as a physiological tumor suppressor and is being investigated fo r clinical applications. It has been reported to target rapidly dividing ce lls. We investigated the effects of 2-MeO-E-2 on the growth plate of young rats because normal longitudinal bone growth requires rapid proliferation o f cartilage and endothelial cells. Sexually mature (3-month-old) normal fem ale rats were treated with 2-MeO-E-2 (100 mg/kg/day) for 13 days and it was found to have no effect on uterine weight but reduced serum cholesterol. T he estrogen metabolite had no effect on either cortical or cancellous bone. In contrast, 2-MeO-E-2 dramatically reduced longitudinal bone growth rate at the proximal tibia from 55 +/- 2 to 20 +/- 2 mu m/day (P < 0.001) and gr owth plate thickness from 153 +/- 14 to 70 +/- 6 mu m (P < 0.001). The latt er decrease was due to significant reductions in the height of both the pro liferative (P < 0.001) and the hypertrophic (P < 0.001) zones, These result s in normal female rats demonstrate that 2-MeO-E-2 inhibited longitudinal b one growth but had no effect on either radial bone growth or cancellous bon e turnover. 2-MeO-E-2 was shown by these studies to have the ability to dis criminate between bone and cartilage, as well as between reproductive and n onreproductive estrogen-target tissues. Thus, 2-MeO-E-2 is a naturally prod uced estrogen metabolite that demonstrates unique tissue selectivity.