In vivo regulation of the insulin-like growth factor system of mitogens by human chorionic gonadotropin.
Human chorionic gonadotropin (hCG) is a differentiating agent and chemopreventive in rat DMBA-induced breast carcinogenesis. Insulin-like growth factors (IGFs) are potent mitogens for breast cancer cells. We report that the administration of hCG to female rats resulted in a significant increase in serum IGFBP-3 levels at doses greater than 10 UI and a significant decrease in serum IGF-I levels. Northern blot analysis revealed that hCG inhibited hepatic and mammary IGF-I gene expression at doses greater than 10 UI. Mammary IGFBP-5 and IGFBP-2 gene expression significantly increased at high doses of hCG while IGFBP-4 slightly decreased. Treatments greater than 10 UI of hCG resulted in a significant suppression of mammary IGFBP-3 and IGF-I receptor expression. Since IGFs are potent mitogens and antiapoptotic agents for breast cancer, this newly described activity of hCG may contribute to its antiproliferative properties, particularly with regard to the differentiation and inhibition of mammary tumours seen in animal models.
McGill University Centre for Translational Research in Cancer, Lady Davis Research Institute, Montreal, H3T 1E2 Quebec, Canada.
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D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000096:biosynthesis / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis / Q000097:blood*; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000096:biosynthesis / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D008934:Mitogens / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis
D006063:Chorionic Gonadotropin; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018975:Insulin-Like Growth Factor Binding Protein 5; D008934:Mitogens; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1