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

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 Cɛ (PKCɛ)–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 PKCɛ, 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 PKCɛ–ERK1/2–Pit‐1 pathway being involved in this action.