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

DE PAUL AL; GUTIERREZ S; SABATINO ME; MUKDSI JH; PALMERI CM; SOAJE M; PETITI JP; TORRES AI

EXPERIMENTAL PHYSIOLOGY.

WILEY-BLACKWELL PUBLISHING, INC

Año: 2010 vol. 96.2 p. 226 - 239

0958-0670

Lactotroph cells display morphological and functional heterogeneity, a feature which is closelyrelated to the oestrogenic environment. In this study, we focused on sex-related differences linkedto 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 ofpituitary-specific transcription factor 1 (Pit-1) inthe actionsofEGFin primarypituitary culturesfrommale and female rats. Epidermal growth factor promoted a differential proliferative activityin 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 malesthe number of 5-bromo-2 -deoxyuridine-labelled prolactin cells was only doubled comparedwith control cultures. However, in both models, EGF had a similar effectiveness in promotingprolactin 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 theproliferative effects of EGF, with the PKCε–ERK1/2–Pit-1 pathway being involved in this action.(Received 7 July 2010; accepted after revision 5 November 2010; first published online 12 November 2010)