Activation of PKC epsilon induces lactotroph proliferation through ERK1/2 in response to phorbol ester

The aim of this investigation was to contribute to current knowledge about intracellular mechanisms that are involved in lactotroph cell proliferation, by evaluating the role of PKCα, PKCɛ and extracellular-signal regulated kinase (ERK) 1/2 in response to phorbol 12-myristate13-acetate (PMA). In primary pituitary cultures, the activation of protein kinase C (PKC) by PMA for 15 min stimulated lactotroph proliferation; whereas a prolonged activation for 3–8 h diminished this proliferative effect. The use of PMA for 15 min-activated PKCɛ and ERK1/2, whereas incubation with PMA for 3 h induced PKCα activation and attenuated the PMA-triggered phosphorylation of ERK1/2. The following inhibitors: PKCs (bisindolylmaleimide I), PKCɛ (ɛV1 peptide) and ERK1/2 (PD98059) prevented the mitogenic activity induced by PMA for 15 min. Lactotroph cells stimulated with PMA for 15 min showed a translocation of PKCɛ to membrane compartment and nucleus. These results thus establish that PKCɛ plays an essential role in the lactotroph proliferation induced by PMA by triggering signals that involve ERK1/2 activation.