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 transgeni c mice does not result in increased overall body growth. The IGF-II overexp ression, however, specifically causes growth of the thymus and not of the s pleen. We address the question whether the observed differences in growth i nduction in lymphoid tissues by IGF-II can he related to differences in loc al IGF binding protein (IGFBP) production, using nonradioactive in situ hyb ridization and Northern blot analysis. IGFBP-2, -4, and -5 are expressed in both lymphoid tissues of normal mice. The spleen additionally expresses IG FBP-3 and IGFBP-6. IGFBP-1 expression was not detected. Although the expres sion pattern of the IGFBPs did not change upon TGF-II overexpression, the l evel of expression changed in a specific manner for each IGFBP. In bath the thymus and the spleen of transgenic mice, IGFBP-2 and -5 gene expression w as slightly increased, whereas the level of IGFBP-4 expression was not alte red. In the spleen, IGFBP-6 expression was not altered by IGF-II overexpres sion, 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 pr oteins 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-/p aracrine pathway.