3,5-diiodothyronine mimics the effect of triiodothyronine on insulin-like growth factor binding protein-4 expression in cultured rat hepatocytes.
We have previously demonstrated that triiodothyronine (T(3)) stimulates hepatic IGFBP-4 expression in rats. Since there is evidence that some of the genes whose expression is regulated by T(3) are also sensitive to 3,5-diiodothyronine (T(2)), we used the adult rat hepatocyte model in primary cultures directly exposed to T(2) to evaluate insulin-like growth factor binding protein-4 (IGFBP-4) expression by Northern and Ligand blot analyses in this study. Our results demonstrate that T(2), like T(3), is able to enhance IGFBP-4 mRNA and protein after 12-24 h of incubation. The potency of the two iodothyronines is comparable as judged by dose-dependence experiments. The T(2)-induced IGFBP-4 increase is independent from ongoing protein synthesis but dependent on active transcription. Since T(3) and T(2) do not affect IGF-I production, it appears that the iodothyronines affect the hepatic IGF system at the IGFBP level. Our data, demonstrating that T(2) mimics the stimulatory effect of T(3) on IGFBP-4 expression by rat hepatocytes, allow us to include IGFBP-4 gene among the genes regulated by the two iodothyronines.
Demori
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Dipartimento di Biologia Sperimentale, Ambientale ed Applicata, Sezione di Fisiologia Generale e Comparata, Università degli Studi di Genova, I-16132 Genova. idemori@unige.it
Gerdoni
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E
Fugassa
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E
Voci
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A
D000818:Animals; D002478:Cells, Cultured; D004104:Diiodothyronines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000235:genetics* / Q000502:physiology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014284:Triiodothyronine / Q000494:pharmacology*
D004104:Diiodothyronines; D018974:Insulin-Like Growth Factor Binding Protein 4; D012333:RNA, Messenger; D014284:Triiodothyronine; C030103:3,5-diiodothyronine