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KMID : 1204320060220040333
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Laboratory Animal Research
2006 Volume.22 No. 4 p.333 ~ p.338
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Effects of Administration of an Anti-sense Oligonucleotide to Insulin-Like Growth Factor-Binding Protein-3 (IGFBP-3) mRNA on Expression of Humoral IGF System Components and Organ Growth in Growing Rats
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Kim Young-Hee
Choi Wan-Sung
Ha Mi-Sook
Kim In-Ae
Jang In-Surk
Lee Chul-Young
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Abstract
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Insulin-like growth factor-binding protein-3 (IGFBP-3) is the major plasma carrier and reservoir of IGF-I which mediates most of the growth-promoting action of growth hormone. The present study was undertaken to examine the effect of administration of a phosphorothioate anti-sense deoxyribouncleotide (AODN; 5``-CATGGCGCTGGCGGAGGGC-3``) targeted to a 5``-untranslated region of IGFBP-3 mRNA in growing rats. After confirming the effectiveness of the AODN in reducing the IGFBP-3 mRNA abundance in C6 rat glial cells in culture, male Sprague-Dawley rats weighing approximately 200 g were intra-peritoneally injected with 0.08-, 0.8-, 8-mg AODN or 8-mg random ODN per kg body weight every 12 h for 3 days. Blood samples were taken from the tail vein on d -1, 0, 1 and 3 of the experiment. Internal organs were excised and weighed at sacrifice following the last blood sampling. Hepatic IGFBP-3 mRNA abundance analyzed by Northern blotting, as well as plasma levels of IGFBP-3 and other IGFBPs resolved by Western ligand blotting, did not differ among the four groups. Plasma IGF-I concentrations tended to increase with increasing doses of the AODN, with 0.09 of p-value for the effect of the treatment. Interestingly, weight of spleen, a most IGF-I-responsive organ, exhibited an identical trend with respect to IGF-I concentration, whereas weights of liver, lung, kidney and heart had no relation to the plasma variable. In summary, the present AODN is judged to be minimally effective in blocking IGFBP-3 translation. Further studies are therefore necessary to find a more effective AODN and also to determine if blood IGF-I concentration and spleen growth have any relation to IGFBP-3 expression.
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KEYWORD
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IGF-I, IGFBP-3, anti-sense oligodeoxyribonucleotide (AODN), rat, growth
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