Prolactin-stimulated ornithine decarboxylase induction in rat hepatocytes: coupling to diacylglycerol generation and protein kinase C.
The trophic effects of prolactin (PRL) in rat liver have been linked to activation of protein kinase C (PKC). Since alterations in PKC activity imply its activation by 1,2-diacylglycerol (DAG), we tested whether PRL treatment stimulated DAG generation coupled to induction of a growth response in primary hepatocytes. Addition of PRL to hepatocyte cultures significantly increased [3H]-glycerol incorporation into DAG within 5 minutes which was followed by a loss of cytosolic PKC activity by 10 minutes. Prolactin also significantly enhanced radiolabel incorporation into triacylglycerol and phospholipids within 10 minutes and induced ODC activity at 6 hours. Therefore, prolactin-stimulated alterations in PKC activity are preceded by enhanced DAG generation. Moreover, these events appear to be coupled to PRL-stimulated entry of hepatocytes into cell cycle.
Buckley
A R
AR
Department of Pharmacology, Kirksville College of Osteopathic Medicine, MO 63501.
Buckley
D J
DJ
D000818:Animals; D004075:Diglycerides / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D005990:Glycerol / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D010743:Phospholipids / Q000378:metabolism; D010928:Placental Lactogen / Q000378:metabolism; D011388:Prolactin / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D014316:Tritium
D004075:Diglycerides; D010743:Phospholipids; D014316:Tritium; D011388:Prolactin; D010928:Placental Lactogen; D011493:Protein Kinase C; D009955:Ornithine Decarboxylase; D005990:Glycerol