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 PKC alpha, PKC epsilon and extracellular-signal regulated kinase (ERK) 1/2 in response to phorbol 12-myristate 13-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 PKC epsilon and ERK1/2, whereas incubation with PMA for 3 h induced PKC alpha activation and attenuated the PMA-triggered phosphorylation of ERK1/2. The following inhibitors: PKCs (bisindolylmaleimide 1), PKC epsilon (epsilon V1 peptide) and ERK1/2 (PD98059) prevented the mitogenic activity induced by PMA for 15 min. Lactotroph cells stimulated with PMA for 15min showed a translocation of PKC epsilon to membrane compartment and nucleus. These results thus establish that PKC epsilon plays an essential role in the lactotroph proliferation induced by PMA by triggering signals that involve ERK1/2 activation. (C) 2008 Elsevier Ireland Ltd. All rights reserved.