Elevated progesterone during pseudopregnancy may prevent bone loss associated with low estrogen

There is increasing evidence for a role of endogenous progesterone in mineral and skeletal metabolism. The purpose of this study was to compare skeletal changes that occur during a condition of high endogenous progesterone but low estrogen (pseudopregnancy) with a condition of low endogenous progesterone and low estrogen (ovariectomy). Pseudopregnancy was selected over pregnancy to eliminate placental factors that may influence mineral metabolism. Rats were ovariectomized (OVX) or pseudopregnancy initiated, and bones were collected 13 days later. In some animals, blood was collected by indwelling catheters for determination of progesterone and estrogen levels. At mid-pseudopregnancy, there were substantial elevations in progesterone but estrogen was below the level of detection. Progesterone and estrogen were below the level of detection in the OVX rats. Longitudinal growth rates were increased compared with the normal cycling rats in both the pseudopregnant and OVX groups, indicative of decreased estrogen levels, but they were greatest in the OVX rats. Cancellous bone mass was maintained in the pseudopregnant rats compared with normal cycling rats but significantly reduced in the OVX animals. As expected, increased bone formation and turnover rates were observed in the OVX animals although some indices of bone formation were also increased in the pseudopregnant animals. Osteoclasts were significantly increased in the OVX but not the pseudopregnant animals compared with normal cycling rats. Increased periosteal bone formation indices are known to occur following OVX, but the greatest periosteal formation rates were observed in the pseudopregnant animals. While possible roles for some other endocrine agents cannot be excluded at this time, the data from the present study suggest that endogenous progesterone may have a role in the maintenance of bone mass perhaps by decreasing bone resorption while maintaining or increasing bone formation during physiological periods of low estrogen such as occurs during early pregnancy.