Role of PI3K/Akt and p38 MAPK in the apoptotic and antiproliferative actions of prolactin on lactotropes

N. DE DIOS; S.ORRILLO; M.IRIZARRI; F.GOTTARDO; F.BOUTILLON; A. SEILICOVICH; V. GOFFIN; D. PISERA; J.FERRARIS

Congreso; LXI Reunión de la Sociedad Argentina de Investigación Clínica; 2016

Prolactin (PRL) induces apoptosis and inhibits proliferation of lactotropes, regulating anterior pituitary homeostasis. Our results suggest that those effects are mediatedby JAK2/STAT5 and ERK1/2 pathways. As the PRL receptor (PRLR) can activate other cascades, we now evaluated whether the actions of PRL on lactotropes depends on themodulation of PI3K/AKT and P38 MAPK, two pathways known to regulate lactotropes homeostasis. To that aim we used the somatolactotrope cell line GH3. Since thesecells secrete PRL constitutively, the paracrine/autocrine effect of PRL was studied using a PRLR antagonist (Δ1?9-G129R-hPRL, APRLR, 5μg/ml, 6h). We determined P38and Akt phosphorylation in the presence or absence of the APRLR (0-240´) by western blot. APRLR did not change significantly Akt phosphorylation but it decreased thep-P38 MAPK. In other experiments, cells were incubated with APRLR in the presence or absence of Akt or P38 inhibitors. Inhibition of PI3K/Akt (LY94007, 10 μM, 6h)increased GH3 cell apoptosis (TUNEL-positive), and inhibited the antiapoptotic effect exerted by the APRLR (C:1.2%, APRLR 0.7% LY: 2.6%,APRLR+LY: 1.7% p