Selective suppression of glutathione S-transferase activities in rat primary hepatocytes by growth hormone.
Glutathione S-transferases (GSTs) detoxify diverse electrophilic chemicals, including anticancer drugs. Containing at least 100 microM total GST, the adult rat liver has abundant alpha and mu class GST isoenzymes. We utilized primary cultured rat hepatocytes, maintained in chemically defined medium, to examine direct regulation of GST activities by human growth hormone (hGH). Maintenance of GST activities in this primary cultured hepatocyte system for 8 days allowed subsequent study of GST regulation by hGH. Protein concentration, cell number, DNA content, and viability did not significantly differ (p > 0.05) between the untreated and hGH (2 micrograms/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 corroborate our findings, we examined phenobarbital induction of GST activities and hGH regulation of certain cytochrome P450-dependent testosterone hydroxylases.
Grgurevich
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Department of Pharmacology Pennsylvania State University, Milton S. Hershey Medical Center, Hershey 17033, USA.
Greene
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D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000378:metabolism
D004791:Enzyme Inhibitors; D013739:Testosterone; D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D005982:Glutathione Transferase; D010634:Phenobarbital