Cell-specific localization of insulin-like growth factor binding protein mRNAs in rat liver

The liver is a major source of circulating insulin-like growth factor I (IG F-I), and it also synthesizes several classes of IGF binding proteins (IGFB Ps). Synthesis of IGF-I and IGFBPs is regulated by hormones, growth factors , and cytokines. They are nutritionally regulated and expressed in developm entally specific patterns. To gain insight into cellular regulatory mechani sms that determine hepatic synthesis of IGF-I and IGFBPs and to identify po tential target cells for IGF-I within the Liver, we studied the cellular si tes of synthesis of IGF-I, IGF receptor, growth hormone (GH) receptor, and IGFBPs in freshly isolated rat hepatocytes, endothelial cells, and Kupffer cells. We also localized cellular sites of IGFBP synthesis by in situ hybri dization histochemistry. Western ligand and immunoblot analyses were used t o determine IGFBP secretion by isolated cells. Two IGF-I mRNA subtypes with different 5' ends (class 1 and class 2) were detected in all isolated live r cell preparations. Type 1 IGF receptor mRNA was detected in endothelial c ells, indicating that these cells are a local target for IGF actions in liv er. GH receptor was expressed in all cell preparations, consistent with GH regulation of IGF-I and IGFBP synthesis in multiple liver cell types. The I GFBPs expressed striking cell-specific expression. IGFBP-1 was synthesized only in hepatocytes, and IGFBP-3 was expressed in Kupffer and endothelial c ells. IGFBP-4 was expressed at high levels in hepatocytes and at low levels in Kupffer and endothelial cells. Cell-specific expression of distinct IGF BPs in the liver provides the potential for cell-specific regulation of hep atic and endocrine actions of IGF-I.