INBIOMED   24026
INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Prolactin receptor signaling pathways involved in anterior pituitary proliferation and apoptosis
Autor/es:
J. FERRARIS; M.IRIZARRI; V. GOFFIN; S.ORRILLO; A. SEILICOVICH; N. DE DIOS; F.GOTTARDO; D. PISERA
Reunión:
Congreso; 98º Annual Meeting of the Endocrine Society; 2017
Resumen:
Prolactin (PRL) induces apoptosis and inhibits proliferation of lactotropes, thereby playing a key role in the regulation of anterior pituitary homeostasis1. Our recent results suggested that these atypical PRL effects involved JAK2 and ERK1/2 kinases2. Since PRL-activated JAK2 can phosphorylate different STAT proteins, we here determined the participation of STAT5 and STAT3 in the apoptotic and antiproliferative effects of PRL. As the PRL receptor (PRLR) activates various other signaling cascades, we also evaluated the involvement of P38 MAPK, a kinase known to regulate lactotrope homeostasis. For these studies, we used i) the GH3 somatolactotrope cell line as a model of PRL-secreting pituitary cells leading to constitutively activated PRLR signaling, ii) the pure PRLR antagonist ∆1?9-G129R-hPRL as a pan-inhibitor of PRLR signaling cascades, and iii) cascade-specific inhibitors targeting STAT5 (U51573108), STAT3 (jsi-124) or P38 (SB203580), whose efficacy and specificity was evaluated by immunofluorescence (p-STAT5 and p-STAT3) or immunoblotting (p-P38 MAPK) using phospho-specific antibodies. Then, we evaluated the effects of all these signaling inhibitors on GH3 cell apoptosis (TUNEL assay) and proliferation (BrdU incorporation). Together, our results suggest that PRL induces apoptosis through the activation of JAK2/STAT5 and p38 MAPK pathways, whereas its antiproliferative effect is mediated by JAK2/STAT5, JAK2/STAT3, and P38 MAPK pathways.