Somatomedin Synthesis by a Subclone of Buffalo Rat Liver Cells: Characterization and Evidence for Immediate Secretion ofde NovoSynthesized Hormone*

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Abstract
Cultured Buffalo rat liver (BRL-3A) cells synthesize and release a somatomedin called multiplication-stimulating activity, a major component of which is rat insulin-like growth factor-II (rIGF-II). A subclone of hepatocytes (BRL-3SC) was isolated from these cells, which release rIGF-II into serum-free medium at a similar but considerably more uniform rate than BRL-3A cells, and their morphology was described and some of the conditions regulating the rate of synthesis and secretion of rIGF-II were defined. Time-course experiments indicate that after a 2-h lag, rIGF-II is released at a nearly constant rate of 70 .mu.U insulin-like activity/ml.cntdot.24 h for 5 days. These cells demonstrate considerable resistance to variations in environmental pH, with extremes of pH 6.8-8.0 in the initial culture medium causing a negligible effect on rIGF-II release. No evidence was found for the existence of an appreciable amount of intracellular rIGF-II, consistent with the lack of secretion granules in these cells. Moreover, at concentrations not causing irreversible cell damage, inhibitors of protein synthesis, cycloheximide and actinomycin D produced 87% and 76% reductions, respectively, in rIGF-II release in 24 h, and inhibitors of oxidative phosphorylation, dinitrophenol and sodium azide reduced rIGF-II release by 72% and 78%, respectively. BRL-3A cells, and particularly those of the subclone BRL-3SC herein described, may provide an excellent model for investigations of somatomedin synthesis and release, and such studies are facilitated by the fact that rIGF-II released into serum-free sodium appears to be the immediate product of de novo peptide synthesis.

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