SPI-1 - AN HEPATIC SERINE-PROTEASE INHIBITOR REGULATED BY GH AND OTHER HORMONES

A sensitive RNAse protection method was used to show that serine prote ase inhibitor-1 (Spi-1) is expressed in rat liver and heart, but not i n kidney or brain. Bovine somatotropin (bGH) and placental lactogen (b PL) induced rat hepatocyte cultures to express both Spi-1 and IGF-1 mR NA, with bPL approximately 100-fold more potent than bGH. Bovine prola ctin (bPrL) did not induce hepatocyte Spi-1 mRNA, demonstrating lack o f involvement of lactogenic receptors. Albumin mRNA levels were stable during hepatocyte culturing and were unaffected by growth hormone (GH ) treatment, showing that neither culture conditions nor GH treatment affected cellular differentiation. Eliminating serum-free medium hormo ne supplements one at a time, estradiol, testosterone and T-3 were sho wn to be unnecessary for GH induction of Spi-1, while dexamethasone re moval decreased Spi-1 mRNA levels to 10% of GH-stimulated controls. bG H induction of Spi-1 mRNA in the presence of only dexamethasone and gl ucagon was 75% higher (p < 0.01) than levels seen with insulin also pr esent.