No abstract

Previously, we have observed that epidermal growth factor (EGF), a potent mitogen for cultured hepatocytes, stimulates the production of IGF-I and IGF-binding proteins (IGFBPs) by cultured hepatocytes from adult rats. This study was undertaken to investigate the possibility that other growth factors of hepatic origin could specifically be involved in the regulation of IGF-I and IGFBP expression. The effects of transforming growth factor-a (TGF-a), through EGF receptors to induce a mitogenic response, and transforming growth factor-b 1 (TGF-b 1 ), produced by non-parenchymal liver cells and able to inhibit hepatocyte proliferation in vivo and in culture, have been studied in cultured adult rat hepatocytes.Our results demonstrate that TGF-a and TGF-b 1 significantly stimulate IGF-I and IGFBP secretion by cultured hepatocytes but no change in the abundance of IGF-I and IGFBP mRNAs was observed with respect to controls. Cycloheximide is able to inhibit both basal and TGF-stimulated release of IGF-I and a similar effect was elicited by octreotide, the somatostatin analog, known to directly affect hepatic IGF-I gene expression.Our findings show the role of the liver in the secretion of IGF-I and IGFBPs, not only under endocrine and nutritional control but also under autocrine and paracrine control.

Gammaglutamyltranspeptidase (GGT) activity is considered as a marker of liver phenotype, being maximally expressed in fetal liver and virtually absent in adult mature tissue. Since thyroid hormone has been identified to influence growth and development of almost all tissues, we have investigated the possible involvement of such factors in regulating rat hepatic GGT. Our results indicate that the activity of GGT in liver of perinatal hypothyroid rats is low as well as in control animals; instead, it is greatly increased in adult hypothyroid rats compared to controls of the same age (+260% in 2-month-old hypothyroid rats). Replacement therapy with T3 to hypothyroid rats normalizes the enzyme activity to the levels of control animals. Thyroid hormone appears to modulate the gene expression of the enzyme, since in the different thyroid status GGT mRNA level closely parallels the variations of the enzyme activity. These results further suggest that thyroid hormone plays a crucial role in maintaining the phenotype of adult liver tissue.

No abstract