title: Dehydroepiandrosterone-dependent induction of peroxisomal proliferation can be reduced by aspartyl esterification without attenuation of inhibitory bone loss in ovariectomy animal model.
abstract: The purpose of this study was to determine whether esterification of dehydroepiandrosterone with aspartate (DHEA-aspartate) could reduce peroxisomal proliferation induced by DHEA itself, without loss of antiosteoporotic activity. Female Sprague-Dawley rats were ovariectomized, then DHEA or DHEA-aspartate 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 excretion was not significantly increased by DHEA or DHEA-aspartate treatment in ovariectomized rats, while it was significantly increased by ovariectomy. Osteocalcin concentration and alkaline phosphatase activity in serum and cross linked N-telopeptide type I collagen level in urine were not significantly different between DHEA-aspartate and DHEA treated groups. DHEA-aspartate treatment significantly reduced liver weight and hepatic palmitoyl-coA oxidase activity compared to DHEA treatment. DHEA-aspartate treatment maintained a nearly normal morphology of peroxisomes, while DHEA treatment increased the number and size of peroxisomes in the liver. According to these results, 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.
authors.affiliation: Aging and Physical Culture Research Institute, Seoul National University, Korea. kwakcs@snu.ac.kr
authors.forename: C S
authors.initials: CS
authors.lastname: Kwak
authors.forename: C M
authors.initials: CM
authors.lastname: Kang
authors.forename: H S
authors.initials: HS
authors.lastname: Kang
authors.forename: K Y
authors.initials: KY
authors.lastname: Song
authors.forename: M S
authors.initials: MS
authors.lastname: Lee
authors.forename: S C
authors.initials: SC
authors.lastname: Seong
authors.forename: S C
authors.initials: SC
authors.lastname: Park
mesh_terms: D042964:Acyl-CoA Dehydrogenase; D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015415:Biomarkers; D002118:Calcium / Q000097:blood / Q000652:urine; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003687:Dehydroepiandrosterone / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004195:Disease Models, Animal; D004951:Esterification; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005260:Female; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D009929:Organ Size; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D010052:Ovariectomy; D020675:Peroxisomes / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000378:metabolism / Q000473:pathology; D014280:Triglycerides / Q000097:blood
chemical_list: D000276:Adjuvants, Immunologic; D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D001224:Aspartic Acid; D003687:Dehydroepiandrosterone; D044943:Fatty Acid Desaturases; D042964:Acyl-CoA Dehydrogenase; D002118:Calcium