NICOLA JUAN PABLO
Congresos y reuniones científicas
Título:
Non-classical testosterone signaling implications in prostate smooth muscle cell proliferation and muscle cell phenotype
Autor/es:
PEINETTI, N; LEIMGRUBER, C; CUELLO RUBIO, M; SCALERANDI, MV; NICOLA, JP; QUINTAR, A; MALDONADO, C
Lugar:
Mar del Plata
Reunión:
Congreso; LXI Reunión científica anual de la Sociedad Argentina de Investigación Clínica; 2016
Institución organizadora:
Sociedad Argentina de Investigación Clínica
Resumen:
Testosterone (T) effects are mediated by a classical pathway
that takes place through the binding of T to the classical androgen
receptor (AR) and migration to the nucleus, and by non-classical
signaling pathways which are mediated by cell surface receptors
capable of activating signaling cascades. The differentiation and
proliferation of pSMC as cell as the stroma/epithelium interaction
are essential in the development of prostatic pathologies. our
objectives were to determine the presence of plasma membrane
AR receptors in pSMC and their participation in cell differentiation,
proliferation and growth factors expression. pSMC were obtained
from Wistar rat prostate and stimulated in vitro with T 10-7 M or
the plasma membrane impermeable T-bovine serum albumin
conjugate (T-BSA) 10-7M. Smooth muscle markers and the expression
of FGF7 and TGF-b were evaluated by qPCR, and cell
proliferation was assessed by immunocytochemistry of Ki67, and
confirmed by cell counter; statistical analysis was performed by
ANOVA-Tukey. The AR plasma membrane localization was demonstrated
by immunofluorescence and confocal microscopy, and
by co-localization with the membrane marker concanavalin-A. This
assay was verified by flow cytometry, which showed a population
of membrane AR positive cells of 18.87%. After T-BSA
stimuli, an increased expression of smooth markers calponin and
α-actin was observed 􀀊p􀀞􀀒.􀀒􀀓 vs ctrl􀀋, while vimentin 􀀴􀀰Am 􀁙as
decreased 􀀊p􀀞􀀒.􀀒􀀓 vs ctrl􀀋. T-BSA also increased cell proliferation
after 􀀔􀀖 or 􀀖􀀚 hours stimulation 􀀊p􀀞􀀒.􀀒􀀗 vs ctrl and T􀀋. Meanwhile,
T increased FGF7 and TGF-b, implicated in proliferation and apoptosis
of epithelial cells respectively, at higher levels than T-BSA
􀀊p􀀞􀀒.􀀒􀀓􀀋. These results demonstrated the presence of membrane
receptors and the participation of non-classical signaling mediating
T-induced pSMC proliferation and differentiation; genomic effects
were stronger modulators of growth factors implicated prostate
cell communication.