The Response of Prostate Smooth Muscle Cells to Testosterone Is Determined by the Subcellular Distribution of the Androgen Receptor

SCALERANDI, MARÍA VICTORIA; PEINETTI, NAHUEL; CUELLO RUBIO, MARIANA MICAELA; TORRES, ALICIA INES; LEIMGRUBER, CAROLINA; NICOLA, JUAN PABLO; MALDONADO, CRISTINA ALICIA; QUINTAR, AMADO ALFREDO

ENDOCRINOLOGY

ENDOCRINE SOC

Año: 2018 vol. 159 p. 945 - 956

0013-7227

Androgen signaling in prostate smooth muscle cells (pSMCs) is critical for the maintenance of prostate homeostasis, with its alterations being a central aspect in the development of pathological conditions. Testosterone can act through the classical androgen receptor (AR) in the cytoplasm eliciting genomic signaling, or through different types of receptors located at the plasma membrane for nongenomic signaling. We here aimed to evidence nongenomic testosterone-signaling mechanisms in pSMCs and their participation in cell proliferation, differentiation, and the modulation of the response to lipopolysaccharide. We demonstrated that pSMCs can respond to testosterone by a rapid activation of ERK1/2 and Akt. Furthermore, a pool of ARs localized at the cell surface of pSMCs is responsible for a nongenomic testosterone-induced increase in cell proliferation. Through membrane receptor stimulation, testosterone favors a muscle phenotype, evidenced trough an increase in smooth muscle markers. In addition, we showed that the anti-inflammatory effects of testosterone, capable of attenuating lipopolysaccharide-induced proinflammatory actions, are promoted only by receptors located inside the cell. We postulate that testosterone might perform pro-homeostatic effects through intracellular-initiated mechanisms, by modulating cell proliferation and inflammation, while some pathological, hyperproliferative actions would be induced by membrane-initiated nongenomic signaling in pSMCs.