Dehydroepiandrosterone-dependent induction of peroxisomal proliferation can be reduced by aspartyl esterification without attenuation of inhibitory bone loss in ovariectomy animal model

The purpose of this study was to determine whether esterification of dehydr oepiandrosterone with aspartate (DHEA-aspartate) could reduce peroxisomal p roliferation induced by DHEA itself, without loss of antiosteoporotic activ ity. Female Sprague-Dawley rats were ovariectomized, then DHEA or DHEA-aspa rtate was administered intraperitoneally at 0.34 mmol/kg BW 3 times a week for 8 weeks. DHEA-aspartate treatment in ovariectomized rats significantly increased trabeculae area in tibia as much as DHEA treatment. Urinary Ca ex cretion was not significantly increased by DHEA or DHEA-aspartate treatment in ovariectomized rats, while it was significantly increased by ovariectom y. Osteocalcin concentration and alkaline phosphatase activity in serum and cross linked N-telopeptide type 1 collagen level in urine were not signifi cantly different between DHEA-aspartate and DHEA treated groups. DHEA-aspar tate treatment significantly reduced liver weight and hepatic palmitoyl-coa oxidase activity compared to DHEA treatment. DHEA-aspartate treatment main tained a nearly normal morphology of peroxisomes, while DHEA treatment incr eased the number and size of peroxisomes in the liver. According to these r esults, it is concluded that DHEA-aspartate ester has an inhibitory effect on bone loss in ovariectomized rats with a marked reduction of hepatomegaly and peroxisomal proliferation compared to DHEA.