Evidence that growth hormone stimulates protein kinase C activity in isolated rat hepatocytes.
The mechanism of action of growth hormone (GH) is not known, although indirect evidence suggests that protein kinase C (PKC) might play an important role in the insulin-like actions of GH. In this investigation, we directly examined the effects of GH relative to those of insulin on PKC activity in isolated rat hepatocytes. Human GH (10(-7) mol/L) significantly increased the activity of PKC in both cytosolic and particulate fractions. The effect was maximal at 1 minute, disappeared at 5 minutes, and then increased again at 30 minutes in both fractions. At 1 minute, maximal and half-maximal stimulation of PKC activity occurred at hGH concentrations of 10(-7) and 5 x 10(-9) mol/L, respectively. Insulin (10(-7) mol/L) also induced a significant and transient increase in enzyme activity at 2 minutes in cytosolic and particulate fractions; at 30 minutes, PKC activity was decreased in the soluble fraction (-17%) and increased in the particulate fraction (+65%). Measurement of specific [3H]-phorbol dibutyrate (PDBu) binding suggested translocation of PKC from the cytosol to the membrane fraction after 30 minutes of incubation, only after insulin treatment. The early effects of GH and insulin on PKC activity were additive in both the particulate and cytosolic fractions. Although the later effects of GH and insulin on PKC were quite different, both hormones rapidly activated PKC in isolated hepatocytes, suggesting that PKC might be involved in triggering the insulin-like actions of GH.
Nivet
V
V
Laboratoire d'Endocrinologie, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes, Paris, France.
Clot
J P
JP
Do
X T
XT
Barrault
V
V
Prélot
M
M
Durand
D
D
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D013006:Growth Hormone / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008297:Male; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011493:Protein Kinase C / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014316:Tritium
D007328:Insulin; D014316:Tritium; D015240:Phorbol 12,13-Dibutyrate; D013006:Growth Hormone; D011493:Protein Kinase C