THE GPCR-Gai REGULATED THE FGF2-INDUCED LACTOTROPH AND SOMATOTROPH CELL PROLIFERATION

SOSA L.; PICECH F.; DE PAUL A.L.; PETITI J. P.; TORRES A.

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAI SAFIS 2018; 2018

In a previous study, we demonstrated that the co-incubation of basic fibroblast growth factor (FGF2) with the analog of somatostatin, octreotide (OCT) induced G1-phase arrest in pituitary cells, suggesting that the somatostatin receptors, inhibitory G protein-coupled receptors (GPCR-Gai), may regulate the FGF2 effects. The aim was to evaluate whether the FGF2 proliferative activity is regulated by GPCR-Gai specifically in lactotroph and somatotroph cell population. Anterior pituitary cell cultures from female rats were treated with FGF2 (10 ng/mL) or OCT (100mM) alone or co-incubated with or without pertussis toxin (PTX, 500nM), an inhibitor of GPCR-Gai. The lactotroph and somatotroph cell proliferation was analyzed by double-immunocytochemistry of BrdU and PRL or GH at 24 and 48h. The p-ERK1/2, c-Jun and cell cycle regulation proteins: cyclin D1, CDK4, p21 and p27 were determined by western blot. Statistics: ANOVA-Bonferrony. The percentage of BrdU/lactotroph positive cells was 7.2% and BrdU/somatotroph positive cells was 3.4%. The lactotroph and somatotroph cell proliferation was increased by FGF2 whereas OCT decreased the cell mitosis respect to control group. The FGF2/OCT co-incubation significantly decreased the proliferation in both cells types after 24 and 48 h respect to FGF2 group, effect that was reverted by pre-incubation with PTX. The diminution in the cell proliferation was associated with an increase in the cell cycle inhibitors p27 and p21 expression, and a decrease of cycle D1 while the CDK4 did not show any significant variation. In addition, a remarkable decrease of pERK1/2 and c-Jun expression was observed after combined treatments. These findings show that OCT treatment inhibited the proliferation induced by FGF2 in PRL and GH cell populations regulating the expression of pERK1/2, c-Jun and key proteins controlling the cell cycle progression. This regulatory effect, mediated for GPCR-Gαi, could participate in the homeostasis of lactotroph and somatotroph cells, principal pituitary cell populations.