Department of Pharmacology and Therapeutics , University of South Florida College of Medicine , Tampa .
J Cell Physiol 148 : 133-8 ( 1991)
Abstract
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 -(-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 .