Epidermal growth factor induces a sexually dimorphic proliferative response of lactotroph cells through protein kinase C-ERK1/2-Pit-1-in vitro

Abstract

Lactotroph cells display morphological and functional heterogeneity, a feature which is closely related to the oestrogenic environment. In this study, we focused on sex-related differences linked to the proliferative and secretory responses of lactotrophs exposed to epidermal growth factor (EGF)-in vitro. Furthermore, we addressed the involvement of the protein kinase Cε (PKCε)-extracellular signal-regulated kinase 1/2 (ERK1/2) signalling pathway and the contribution of pituitary-specific transcription factor 1 (Pit-1) in the actions of EGF in primary pituitary cultures from male and female rats. Epidermal growth factor promoted a differential proliferative activity in prolactin cells, which was strongly sex related, as revealed by the uptake of 5-bromo-2'-deoxyuridine. In females, the mitogenic activity was up to nine times greater, whereas in males the number of 5-bromo-2'-deoxyuridine-labelled prolactin cells was only doubled compared with control cultures. However, in both models, EGF had a similar effectiveness in promoting prolactin secretion. Epidermal growth factor also induced a significant increase in the PKCε, phosphorylated ERK1/2 and Pit-1 protein levels, which were higher in females than in males. Pre-incubation with bisindolylmaleimide I blocked EGF-induced ERK1/2 activation and Pit-1 expression. These results suggest a sexually dimorphic response of lactotroph cells to the proliferative effects of EGF, with the PKCε-ERK1/2-Pit-1 pathway being involved in this action. © 2010 The Authors. Journal compilation © 2011 The Physiological Society.