Intracellular Pathways Involved in the Apoptotic and Antiproliferative Actions of Prolactin on Lactotropes

NATALY DE DIOS; MARTIN IRIZARRI; SANTIAGO JORDI ORRILLO; MARIA FLORENCIA GOTTARDO; FLORENCE BOUTILLON; JULIA HALPERIN; ADRIANA SEILICOVICH; VINCENT GOFFIN; DANIEL PISERA; JIMENA FERRARIS

Boston

Congreso; 98th Annual Meeting and Expo of the Endocrine Society; 2016

Endocrine Society

In contrast to what is observed in many other target tissues, prolactin (PRL) induces apoptosis and inhibitsproliferation of lactotropes, which is assumed to maintain anterior pituitary homeostasis (1,2). Our aim wasto identify the signaling pathways involved in these unusual effects. Since somatolactotrope GH3 cells andlactotropes secrete PRL constitutively, we used a pure PRL receptor antagonist (Δ1?9-G129R-hPRL) toinhibit all the PRL receptor-mediated effects. GH3 cells and rat anterior pituitary primary cell cultures wereincubated with Δ1?9-G129R-hPRL in the presence or in the absence of various kinase inhibitors targetingcanonical signaling pathways of the PRL receptor (AG490, a JAK2 inhibitor, and PD98950, a MEKinhibitor). We determined the phosphorylation status of STAT5, ERK1/2 and Akt and the expression of Baxand Bcl-2 by western blot. Phospho-STAT5 was also analyzed using immunofluorescence. We used GH3cells to evaluate the effects of kinase inhibitors and/or Δ1?9-G129R-hPRL on cell apoptosis(hypodiploidy-FACS and TUNEL assay) and proliferation (BrdU incorporation). Together, our results suggestthat PRL induces apoptosis through the activation of MEK-related pathways and the regulation of thebalance of Bcl-2 family proteins. On the other hand, JAK2/STAT5 may mediate the antiproliferative effect ofPRL on anterior pituitary cells.