ROLE OF PI3K/AKT AND P38 MAPK IN THE APOPTOTIC AND ANTIPROLIFERATIVE ACTIONS OF PROLACTIN ON LACTOTROPES

DE DIOS NATALY; SANTIAGO JORDI ORRILLO; GOTTARDO MF; BOUTILLO FLORENCE; SEILICOVICH A; VICENT GOFFIN; PISERA D; FERRARIS J

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Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA; 2016

Prolactin (PRL) induces apoptosis and inhibits proliferation oflactotropes, regulating anterior pituitary homeostasis. Our resultssuggest that those effects are mediated by JAK2/STAT5 andERK1/2 pathways. As the PRL receptor (PRLR) can activate othercascades, we now evaluated whether the actions of PRL on lactotropesdepends on the modulation of PI3K/AKT and P38 MAPK,two pathways known to regulate lactotropes homeostasis. To thataim we used the somatolactotrope cell line GH3. Since thesecells secrete PRL constitutively, the paracrine/autocrine effect ofPRL was studied using a PRLR antagonist (Δ1?9-G129R-hPRL,APRLR, 5μg/ml, 6h). We determined P38 and Akt phosphorylationin the presence or absence of the APRLR (0-240´) by westernblot. APRLR did not change significantly Akt phosphorylation butit decreased the p-P38 MAPK. In other experiments, cells wereincubated with APRLR in the presence or absence of Akt or P38inhibitors. Inhibition of PI3K/Akt (LY94007, 10 μM, 6h) increasedGH3 cell apoptosis (TUNEL-positive), and inhibited the antiapoptoticeffect exerted by the APRLR (C:1.2%, APRLR 0.7% LY:2.6%, APRLR+LY: 1.7% p