Differential actions of testosterone on prostate smooth muscle cells in accordance with the subcellular localization of the AR

PEINETTI NAHUEL; SCALERANDI MV; MALDONADO CA; LEIMGRUBER C; QUINTAR AA; CUELLO RUBIO MARIANA MICAELA; NICOLA JUAN PABLO

Buenos Aires

Congreso; LXII Reunión Científica Anual de la Sociedad Argentina de Investigaciones Clínicas; 2017

Sociedad Argentina de Investigación Clínica (SAIC)

(1508) DIFFERENTIAL ACTIONS OF TESTOSTERONE ON PROSTATE SMOOTH MUSCLE CELLS IN ACCORDANCE WITH THE SUBCELLULAR LOCALIZATION OF THE ANDROGEN RECEPTORNahuel Peinetti, Mariana Micaela Cuello Rubio, Carolina Leimgruber, Maria Victoria Scalerandi, Juan Pablo Nicola, Amado Alfredo Quintar, Cristina Alicia Maldonado Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.Testosterone (T) actions in prostate smooth muscle cells (pSMCs) are critical for prostate homeostasis and the development of pathological conditions. T can operate through the classical cytoplasmic androgen receptor (AR) eliciting genomic signaling, or via receptors located at the plasma membrane for nongenomic signaling. Here we aimed to evidence nongenomic T signaling in pSMCs and their role in cell proliferation, differentiation, and modulation of lipopolysaccharide (LPS)-induced response. For this purpose rat pSMCs were stimulated with T or BSA-conjugated T (T-BSA). To analyze modulation of LPS-response, pSMCs were stimulated with LPS, LPS+T or LPS+T-BSA. ANOVA-Tuckey was used for statistical analysis Membrane localization of AR in pSMCs was determined by confocal microscopy and flow-cytometry with anti-AR antibody, and verified by western blot (WB) of isolated cell surface proteins. Furthermore, we showed that pSMCs can respond to T or T-BSA by nongenomic activation of ERK1/2 and Akt phosphorylation, as evidenced by WB. Membrane stimulation with testosterone resulted in AR- and pERK- dependent increase in cell proliferation (Ki67 and total cell count) which was determined by the use of specific inhibitors (p