SELECTIVE SUPPRESSION OF GLUTATHIONE-S-TRANSFERASE ACTIVITIES IN RAT PRIMARY HEPATOCYTES BY GROWTH-HORMONE

Glutathione S-transferases (GSTs) detoxify diverse electrophilic chemi cals, including anticancer drugs. Containing at least 100 mu M total G ST, the adult rat liver has abundant alpha and mu class GST isoenzymes . We utilized primary cultured rat hepatocytes, maintained in chemical ly defined medium, to examine direct regulation of GST activities by h uman growth hormone (hGH). Maintenance of GST activities in this prima ry cultured hepatocyte system for 8 days allowed subsequent study of G ST regulation by hGH. Protein concentration, cell number, DNA content, and viability did not significantly differ (p > 0.05) between the unt reated and hGH (2 mu g/ml)-treated hepatocytes. However, hGH treatment decreased mu GST activity (p < 0.05), whereas alpha GST activity was unaltered. As positive controls for our culture system and to corrobor ate our findings, we examined phenobarbital induction of GST activitie s and hGH regulation of certain cytochrome P450-dependent testosterone hydroxylases.