Extracellular-signal regulated kinase regulates production of pro-opiomelanocortin in pituitary melanotroph cells.

The extracellular signal-regulated kinase (ERK) pathway is important in the regulation of neuronal plasticity, although a role for the kinase in regulating plasticity of neuroendocrine systems has not been examined. The melanotroph cells in the pars intermedia of pituitary gland of the amphibian Xenopus laevis are highly plastic, undergoing very strong growth to support the high biosynthetic and secretory activity involving alpha-melanophore-stimulating hormone (alpha-MSH), a peptide that causes pigment dispersion in dermal melanophores during the adaptation of the animal to a dark background. In the present study, we tested our hypothesis that ERK-signalling is involved in the regulation of melanotroph cell function during black-background adaptation, namely in the production of pro-opiomelanocortin (POMC), the precursor of a-MSH. Using western blot analyses, we found elevated levels of the activated (phosphorylated) form of ERK in melanotrophs of black- versus white-adapted animals. Treatment of melanotrophs in vitro with the mitogen-activated protein kinase kinase inhibitor U0126 markedly reduced ERK phosphorylation and lowered the transcription as well as the translation of POMC. This same treatment also reduced the expression of BDNF transcript IV and of the immediate early genes c-Fos and Nur77. We conclude that ERK-mediated signalling is important for the maintenance of the melanotroph cells in an active state.