Prolactin induces proliferation of vascular smooth muscle cells through a protein kinase C-dependent mechanism.
The effects of prolactin (PRL) on A10 (aortic smooth muscle) cell proliferation were examined by measuring both [3H]thymidine incorporation and increases in cell number. PRL induced a significant proliferative response from 10(-11) to 10(-7) M, with optimal activity at 10(-10) M. PRL also enhanced platelet-derived growth factor (PDGF)-induced proliferation. The possibility that PRL induces proliferation through a protein kinase C (PKC)-mediated mechanism was also examined. PRL caused activation of PKC from 10(-12) to 10(-8) M. Antiserum to PRL, a monoclonal antibody directed against the PRL receptor and the immunosuppressive agent cyclosporine A, were able to inhibit PRL-induced proliferation and activation of PKC. The PKC inhibitors, staurosporine, sphingosine, and 1-(-5-iso-quinoline-sulfonyl)-2-methylpiperazine (H-7) also antagonized both proliferation and PKC activation. These data strongly suggest that PRL-induced A10 cell proliferation is mediated through the PKC pathway and that this may play a role in vascular smooth muscle cell hyperplasia, characteristic of the pathogenesis of cardiovascular diseases such as hypertension and atherosclerosis.
Sauro
M D
MD
Department of Pharmacology and Therapeutics, University of South Florida College of Medicine, Tampa.
Zorn
N E
NE
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003524:Cyclosporins / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D007546:Isoquinolines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000201:enzymology / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011388:Prolactin / Q000276:immunology / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D011981:Receptors, Prolactin / Q000187:drug effects / Q000276:immunology; D013110:Sphingosine / Q000494:pharmacology; D019311:Staurosporine; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D000470:Alkaloids; D003524:Cyclosporins; D007546:Isoquinolines; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D011981:Receptors, Prolactin; D014316:Tritium; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011388:Prolactin; D004247:DNA; D011493:Protein Kinase C; D019311:Staurosporine; D013110:Sphingosine; D013936:Thymidine