J Korean Med Sci.  2000 Oct;15(5):533-541. 10.3346/jkms.2000.15.5.533.

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

• Kwak CS
• Kang CM
• Kang HS
• Song KY
• Lee MS
• Seong SC
• Park SC

• KMID: 965875
• DOI: http://doi.org/10.3346/jkms.2000.15.5.533

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.

Keyword

Dehydroepiandrosterone; Aspartic Acid; Osteoporosis; Peroxisomal Proliferation; Ovariectomy

MeSH Terms

Adjuvants, Immunologic/pharmacology*
Adjuvants, Immunologic/metabolism
Adjuvants, Immunologic/chemistry
Animal
Aspartic Acid/pharmacology*
Aspartic Acid/metabolism
Aspartic Acid/chemistry
Biological Markers
Calcium/urine
Calcium/blood
Disease Models, Animal
Esterification
Fatty Acid Desaturases/metabolism
Female
Injections, Intraperitoneal
Lipoproteins, HDL Cholesterol/blood
Lipoproteins, LDL Cholesterol/blood
Liver/enzymology
Liver/drug effects
Organ Weight
Osteoporosis/pathology
Osteoporosis/metabolism*
Osteoporosis/drug therapy*
Ovariectomy*
Peroxisomes/metabolism*
Prasterone/pharmacology*
Prasterone/metabolism
Prasterone/chemistry
Rats
Rats, Sprague-Dawley
Tibia/pathology
Tibia/metabolism
Triglycerides/blood