IGF-I- and IGFBP-3-expression in cultured human preadipocytes and adipocytes.
The expression and secretion of IGF-I and IGFBP-3 were investigated in cultured human preadipocytes and in in vitro differentiated adipocytes derived from human subcutaneous adipose tissue under chemically defined culture conditions. Human preadipocytes expressed mRNAs for IGF-I and IGFBP-3 and secreted the corresponding proteins into the culture medium as measured by sensitive radioimmunoassays. In human adipocytes; specific mRNA-expression was comparable to that found in preadipocytes, but IGF-I secretion was increased 10-fold (3.87 +/- 0.69 vs. 0.41 +/- 0.11 ng/ml/10(6) cells/48 hrs, p < 0.05) and IGFBP-3 secretion 2.5-fold (7.34+/-1.15 vs. 3.27+/-0.38 ng/ml/10(6) cells/48 hrs, p<0.05) in the presence of adipogenic medium probably resulting in an increase of unbound IGF-I. Under serum-free, chemically defined conditions human growth hormone (hGH) and insulin were found to be positive regulators and cortisol was found to be a negative regulator of IGF-I and IGFBP-3 secretion in preadipocytes. In cultured human adipocytes, hGH showed no effect on IGF-I and IGFBP-3 secretion, whereas insulin stimulated and cortisol inhibited the secretion of both proteins. We conclude that IGF-I and IGFBP-3 may not only exert their actions in human adipose tissue via circulation, but also in an auto/paracrine way.
Department of Pediatrics, University of Ulm, Germany. martin.wabitsch@medizin.uni-ulm.de
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Wabitsch
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Heinze
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Debatin
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Blum
D017667:Adipocytes / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D005260:Female; D015870:Gene Expression; D019382:Human Growth Hormone / Q000494:pharmacology; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism*
D016895:Culture Media, Serum-Free; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I