Delivery of mevalonate to murine extrahepatic tissues via mini-osmotic pumps.
BACKGROUND
Mevalonate and derivatives of mevalonate metabolism play important roles in cellular metabolism and may be especially important in rapidly growing cancer cells. A method for delivering mevalonate to extrahepatic tissues, where many tumors of interest in experimental cancer research are found, has not been reported.


METHODS
Mice were administered mevalonate subcutaneously via implanted Alzet mini-osmotic pumps. Microsomes isolated from samples of liver, mammary gland, and colon were assayed for 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity. This enzyme is responsible for endogenous mevalonate synthesis, and its down-regulation is evidence that mevalonate has reached the tissue. Serum cholesterol levels were determined to exclude the possibility that down-regulation of HMG-CoA reductase was caused by an influx of circulating cholesterol.


RESULTS
HMG-CoA reductase activity was decreased in livers, mammary glands, and colons of mice given mevalonate via mini-osmotic pumps. Serum cholesterol levels did not rise in these mice, precluding an indirect effect of serum lipoproteins on HMG-CoA reductase regulation.


CONCLUSIONS
Mevalonate can be effectively delivered to cells of the mammary gland and colon of mice via subcutaneously implanted mini-osmotic pumps.
Duncan
Robin E
RE
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
El-Sohemy
Ahmed
A
Archer
Michael C
MC
D000818:Animals; D002784:Cholesterol / Q000097:blood; D003106:Colon / Q000187:drug effects* / Q000201:enzymology; D005260:Female; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D015918:Infusion Pumps, Implantable; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000201:enzymology; D008798:Mevalonic Acid / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008861:Microsomes / Q000201:enzymology; D008904:Miniaturization
D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D008798:Mevalonic Acid