The progesterone antagonist, RU486 does not affect basal or estrogen-stimulated cancellous bone formation in the rat

Abstract

Although it has been suggested that progesterone may have a role in preventing postmenopausal bone loss, a number of studies have shown that progesterone has no additive effect on estrogen therapy. We have recently found that high-dose estrogen stimulates bone formation in rats. The effect of progesterone on this anabolic action of estrogen has not been tested. We therefore investigated the role of progesterone in combination with endogenous or exogenous estrogen on bone formation in rats using RU486, which has been shown to be a potent progesterone antagonist without detectable agonist effects. Three-month-old Wistar female rats were treated for 17 days with RU486, and histomorphometric indices of bone formation were measured at the proximal tibial metaphysis after administration of double fluorochrome labels. Animals treated with RU486 (10 mg/kg) showed no change in either bone formation rate or double-labelled bone surfaces compared to vehicle-treated controls. Estrogen (17 beta-estradiol, 4 mg/kg) increased both indices by more than double compared with controls. RU486 did not affect the indices of increased bone formation in estrogen-treated rats. Estrogen also exhibited inhibition of longitudinal bone growth, while RU486 had no effect either in normal or estrogen-treated animals. These results show that the progesterone antagonist affects neither the stimulatory effect on formation nor the inhibitory effect on longitudinal bone growth by estrogen. These results suggest that progesterone does not play a significant role in either bone formation or bone growth in the rat.