Insulin-like growth factor (IGF) II induced changes in expression of IGF binding proteins in lymphoid tissues of hIGF-II transgenic mice.
Overexpression of human insulin-like growth factor II (IGF-II) in transgenic mice does not result in increased overall body growth. The IGF-II overexpression, however, specifically causes growth of the thymus and not of the spleen. We address the question whether the observed differences in growth induction in lymphoid tissues by IGF-II can be related to differences in local IGF binding protein (IGFBP) production, using nonradioactive in situ hybridization and Northern blot analysis. IGFBP-2, -4, and -5 are expressed in both lymphoid tissues of normal mice. The spleen additionally expresses IGFBP-3 and IGFBP-6. IGFBP-1 expression was not detected. Although the expression pattern of the IGFBPs did not change upon IGF-II overexpression, the level of expression changed in a specific manner for each IGFBP. In both the thymus and the spleen of transgenic mice, IGFBP-2 and -5 gene expression was slightly increased, whereas the level of IGFBP-4 expression was not altered. In the spleen, IGFBP-6 expression was not altered by IGF-II overexpression, whereas IGFBP-3 expression was strongly increased. The differences in IGFBP expression, and the difference in response of these IGFBPs to IGF-II overexpression in thymus and spleen suggests an important role of these proteins in growth regulation of both lymphoid tissues. We speculate that an increase of IGFBP-3 expression together with changes in expression of other IGFBPs, inhibits IGF-II stimulated growth in the spleen by an autocrine-/paracrine pathway.
Smink
J J
JJ
Department of Pediatric Endocrinology, University Medical Center Utrecht, The Netherlands. J.Smink@wkz.azu.nl
Koster
J G
JG
Hendriks-Stegeman
B I
BI
Van Buul-Offers
S C
SC
D000818:Animals; D015152:Blotting, Northern; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000235:genetics; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000235:genetics; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000502:physiology; D008221:Lymphoid Tissue / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D013154:Spleen / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism
D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D018976:Insulin-Like Growth Factor Binding Protein 6; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II