Antagonic effects of oestradiol in interaction with IGF-1 on proliferation of lactotroph cells in vitro

GUTIÉRREZ SILVINA;; PETITI JUAN PABLO;; DE PAUL ANA;; MUKDSI JORGE;; AOKI AGUSTÍN;; TORRES ALICIA;; ORGNERO ELSA MARGARITA.

HISTOCHEMISTRY AND CELL BIOLOGY.

Springer

Lugar: Heidelberg; Año: 2005 vol. 124 p. 291 - 301

0948-6143

The effects of IGF-1, 17 b oestradiol and its functional interaction on lactotrophs cell proliferation were evaluated. In addition we investigated the involvement of PKC a, e and phosphorilated ERK, in the mitogenic process. Primary cell cultures of adenohypophysis from female Wistar rats were studied in serum free conditions. The proliferation of lactotrophs was determined by double immunostaining for BrdU and PRL. The incubation with IGF-1 5, 30 or 100ng/ml during 48 or 72h increased lactotrophs proliferation 2-3 fold depending on IGF-1 concentration. Co-incubation of IGF-1 (30 ng/ml) with genistein (25ìM) or BIM (0.5 or 2ìM), lowered of tyrosine kinase receptor or of PKC respectively, inhibited the induced IGF-1 lactotrophs proliferation. 17 b oestradiol (1, 10 or 100nM) had not mitogenic effect, whereas in the presence of serum PRL cells proliferation was stimulated. Co-incubation with 1nM oestradiol and IGF-1 significantly decreased the lactotroph BrdU-labelling achieved with IGF-1. PKC a, e and ERK1/2 levels measured by western blot augmented in presence of IGF-1 and were inhibited with the addition of genistein, supporting a participation of these enzymes in the proliferate process. Co-incubation of IGF-1 with 1nM oestradiol decreased both PKC isoforms and activated ERK1/2 levels, suggesting that oestradiol would exert its antiproliferative effect by acting on the signalling pathway of IGF-1. The results revealed antagonic effects of oestradiol on lactotroph proliferation depending on its concentration and the presence of IGF-1.