Regulation of FGF2-induced proliferation by inhibitory GPCR in normal pituitary cells.

Autor:	Sosa LDV; Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Centro de Microscopía Electrónica, Córdoba, Argentina.; Consejo Nacional de Investigaciones Científicas Técnicas (CONICET), Instituto de Investigaciones en Ciencias de la Salud (INICSA), Córdoba, Argentina., Picech F; Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Centro de Microscopía Electrónica, Córdoba, Argentina.; Consejo Nacional de Investigaciones Científicas Técnicas (CONICET), Instituto de Investigaciones en Ciencias de la Salud (INICSA), Córdoba, Argentina., Perez P; Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Centro de Microscopía Electrónica, Córdoba, Argentina.; Consejo Nacional de Investigaciones Científicas Técnicas (CONICET), Instituto de Investigaciones en Ciencias de la Salud (INICSA), Córdoba, Argentina., Gutierrez S; Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Centro de Microscopía Electrónica, Córdoba, Argentina.; Consejo Nacional de Investigaciones Científicas Técnicas (CONICET), Instituto de Investigaciones en Ciencias de la Salud (INICSA), Córdoba, Argentina., Leal RB; Universidade Federal de Santa Catarina, Florianópolis, Departamento de Bioquímica e Programa de Pós-graduação em Bioquímica, Centro de Ciências Biológicas, Santa Catarina, Brazil., De Paul A; Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Centro de Microscopía Electrónica, Córdoba, Argentina.; Consejo Nacional de Investigaciones Científicas Técnicas (CONICET), Instituto de Investigaciones en Ciencias de la Salud (INICSA), Córdoba, Argentina., Torres A; Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Centro de Microscopía Electrónica, Córdoba, Argentina.; Consejo Nacional de Investigaciones Científicas Técnicas (CONICET), Instituto de Investigaciones en Ciencias de la Salud (INICSA), Córdoba, Argentina., Petiti JP; Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Centro de Microscopía Electrónica, Córdoba, Argentina.; Consejo Nacional de Investigaciones Científicas Técnicas (CONICET), Instituto de Investigaciones en Ciencias de la Salud (INICSA), Córdoba, Argentina.
Jazyk:	angličtina
Zdroj:	Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2023 Jul 27; Vol. 14, pp. 1183151. Date of Electronic Publication: 2023 Jul 27 (Print Publication: 2023).
DOI:	10.3389/fendo.2023.1183151
Abstrakt:	Introduction: Intracellular communication is essential for the maintenance of the anterior pituitary gland plasticity. The aim of this study was to evaluate whether GPCR-Gαi modulates basic fibroblast growth factor (FGF2)-induced proliferative activity in normal pituitary cell populations. Methods: Anterior pituitary primary cell cultures from Wistar female rats were treated with FGF2 (10ng/mL) or somatostatin analog (SSTa, 100nM) alone or co-incubated with or without the inhibitors of GPCR-Gαi, pertussis toxin (PTX, 500nM), MEK inhibitor (U0126, 100µM) or PI3K inhibitor (LY 294002, 10 μM). Results: FGF2 increased and SSTa decreased the lactotroph and somatotroph BrdU uptak2e (p<0.05) whereas the FGF2-induced S-phase entry was prevented by SSTa co-incubation in both cell types, with these effects being reverted by PTX, U0126 or LY294002 pre-incubation. The inhibition of lactotroph and somatotroph mitosis was associated with a downregulation of c-Jun expression, a decrease of phosphorylated (p) ERK and pAKT. Furthermore, SSTa was observed to inhibit the S-phase entry induced by FGF2, resulting in a further increase in the number of cells in the G1 phase and a concomitant reduction in the number of cells in the S phases (p< 0.05), effects related to a decrease of cyclin D1 expression and an increase in the expression of the cell cycle inhibitors p27 and p21. Discussion: In summary, the GPCR-Gαi activated by SSTa blocked the pro-proliferative effect of FGF2 in normal pituitary cells via a MEK-dependent mechanism, which acts as a mediator of both anti and pro-mitogenic signals, that may regulate the principal effectors of the G1 to S-phase transition. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Sosa, Picech, Perez, Gutierrez, Leal, De Paul, Torres and Petiti.)
Databáze:	MEDLINE
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