Prolactin induces proliferation of vascular smooth muscle cells through a protein kinase C‐dependent mechanism

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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 1-(-5-isc-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.