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Horm Metab Res 2004; 36(1): 7-13
DOI: 10.1055/s-2004-814176
Original Basic
© Georg Thieme Verlag Stuttgart · New York

Retinoic Acid Increases Insulin-like Growth Factor-binding Protein-4 Expression in Cultured Rat Hepatocytes

I.  Demori1 , S.  Balocco1 , E.  Gerdoni1 , E.  Fugassa1 , A.  Voci1
  • 1Dipartimento di Biologia Sperimentale, Ambientale ed Applicata (DIBISAA), Sezione di Fisiologia Generale e Comparata, Università degli Studi di Genova
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Publication History

Received 15 April 2003

Accepted after revision 7 July 2003

Publication Date:
25 February 2004 (online)

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Abstract

Hepatic insulin-like growth factor binding protein (IGFBP) expression is controlled by diverse factors including thyroid hormone, which enhances IGFBP-4 production in hepatocytes. In the present work, we have investigated whether hepatic IGFBP-4 expression is regulated by retinoic acid (RA), which acts via nuclear receptors belonging to the steroid/thyroid hormone receptor superfamily. Primary cultures of adult rat hepatocytes were incubated with two natural stereoisomers of RA, all-trans RA and 9-cis RA (atRA and 9cRA), and with the synthetic RA receptor (RAR)-selective agonist TTNPB. IGFBP-4 mRNA abundance was measured by Northern blot and protein production was evaluated by Ligand blot on hepatocyte-conditioned culture media. Our results indicate that atRA, 9cRA, and TTNPB increase IGFBP-4 expression by cultured hepatocytes, both at the mRNA and protein level. The RARs play a definite role in this regulation, which is independent from ongoing protein synthesis but dependent on active transcription. AtRA and thyroid hormone act synergistically in increasing hepatic IGFBP-4 expression. Our data establish a role for hormonal factors such as thyronines and retinoids in regulating the hepatic IGF system directly at the IGFBP-4 level.

Key words

Retinoids - IGF - Liver - Nuclear receptors

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E. Fugassa

Dipartimento di Biologia Sperimentale · Ambientale ed Applicata (DIBISAA) · Sezione di Fisiologia Generale e Comparata · Università degli Studi di Genova

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Phone: +39(010)3538243

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