GOTTARDO MarÍa Florencia
congresos y reuniones científicas
Intracellular Pathways Involved in the Apoptotic and Antiproliferative Actions of Prolactin on Lactotropes.
DE DIOS NATALY; MARTIN IRIZARRI; SANTIAGO JORDI ORRILLO; GOTTARDO MF; FLORENCE BOUTILLON; JULIA HALPERIN; SEILICOVICH A; VINCENT GOFFIN; PISERA D; FERRARIS J
Congreso; ENDO annual meeting; 2016
In contrast to what is observed in many other target tissues, prolactin (PRL) induces apoptosis and inhibits proliferation of lactotropes, which is assumed to maintain anterior pituitary homeostasis (1,2). Our aim was to identify the signaling pathways involved in these unusual effects. Since somatolactotrope GH3 cells and lactotropes secrete PRL constitutively, we used a pure PRL receptor antagonist (Δ1?9-G129R-hPRL) to inhibit all the PRL receptor-mediated effects. GH3 cells and rat anterior pituitary primary cell cultures were incubated with Δ1?9-G129R-hPRL in the presence or in the absence of various kinase inhibitors targeting canonical signaling pathways of the PRL receptor (AG490, a JAK2 inhibitor, and PD98950, a MEK inhibitor). We determined the phosphorylation status of STAT5, ERK1/2 and Akt and the expression of Bax and Bcl-2 by western blot. Phospho-STAT5 was also analyzed using immunofluorescence. We used GH3 cells 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 suggest that PRL induces apoptosis through the activation of MEK-related pathways and the regulation of the balance of Bcl-2 family proteins. On the other hand, JAK2/STAT5 may mediate the antiproliferative effect of PRL on anterior pituitary cells.