title: 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 EGF in vitro. Furthermore, we addressed the involvement of the PKCε/ERK1/2 signalling pathway and the contribution of Pit-1 in the EGF actions in primary pituitary cultures from male and female rats. EGF promoted a differential proliferative activity on PRL cells, which was closely associated to the sex, as revealed by the uptake of bromodeoxyuridine (BrdU). In females, the mitogenic activity was up to nine times greater, whereas in males, the number of BrdU-labelled PRL cells was only doubled compared to control. However, in both models, EGF had a similar effectiveness in promoting PRL secretion. EGF also induced a significant increase in the PKCε, P -ERK 1/2, and Pit-1 protein levels, which were higher in females than in males. Pre-incubation with BIM blocked EGF-induced ERK 1/2 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.
authors.affiliation: Universidad Nac de Córdoba, Argentina. adepaul@cmefcm.uncor.edu
authors.forename: Ana Lucía
authors.initials: AL
authors.lastname: De Paul
authors.forename: Silvina
authors.initials: S
authors.lastname: Gutiérrez
authors.forename: María E
authors.initials: ME
authors.lastname: Sabatino
authors.forename: Jorge H
authors.initials: JH
authors.lastname: Mukdsi
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Palmeri
authors.forename: Marta
authors.initials: M
authors.lastname: Soaje
authors.forename: Juan P
authors.initials: JP
authors.lastname: Petiti
authors.forename: Alicia I
authors.initials: AI
authors.lastname: Torres
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D052682:Lactotrophs / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation; D011388:Prolactin / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D017208:Rats, Wistar; D012727:Sex Characteristics; D012737:Sex Factors; D015398:Signal Transduction / Q000187:drug effects; D050817:Transcription Factor Pit-1 / Q000378:metabolism*
chemical_list: C494186:Pou1f1 protein, rat; D050817:Transcription Factor Pit-1; D004815:Epidermal Growth Factor; D011388:Prolactin; C497257:Prkce protein, rat; D051744:Protein Kinase C-epsilon; C535149:Mapk1 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3