El papel de los estrógenos y sus receptores en la prevención y promoción de enfermedades proliferativas de la glándula prostática
Resumen
Resumen
Los estrógenos son hormonas esteroides que actúan a través de sus receptores (RE) α y β, los cuales actúan como factores de transcripción. A pesar de estar implicados principalmente en la fisiología femenina, los estrógenos son importantes en procesos fisiológicos de los machos, existiendo órganos tales como la próstata cuya homeostasis está influenciada por estas hormonas. En próstata, los estrógenos promueven o limitan la proliferación celular dependiendo del receptor activado, lo cual tiene implicaciones en la fisiopatología de la hiperplasia prostática benigna (HPB) y el cáncer prostático (CaP). Existe evidencia de que RE α promueve proliferación mientras que REβ la regula, comportándose como un factor protector de las patologías mencionadas. No obstante, en etapas avanzadas del CaP, la presencia de REβ en células prostáticas se relaciona con mayor proliferación de éstas y aumento en la mortalidad de los pacientes. Es probable que en este caso REβ active vías de señalización andrógeno-independientes que favorecen la proliferación, lo que resultaría importante en la falta de respuesta al tratamiento de supresión androgénica observado frecuentemente en el CaP. Otro aspecto importante sobre REβ es la regulación de su expresión. En este proceso se conoce la participación de las hormonas esteroides, pero existen indicios de que prolactina, una hormona proteica, participa también en contextos fisiológicos y patológicos. El conocimiento de estos y otros aspectos de la acción estrogénica en próstata contribuirá al desarrollo de estrategias para el tratamiento y prevención de HPB y CaP.
Abstract
Estrogens are steroid hormones acting through their receptors (ER) α and β, act as transcription factors. Despite being primarly involved in female physiology, estrogens are important regulators of some males physiological processes, existing organs such as the prostate, which is influenced by these hormones. In prostate, through its α and β RE estrogens promote or limit the cell proliferation in normal conditions, and are implicated in the pathophysiology of benign prostatic hyperplasia (BPH) and prostate cancer (PCa). There is evidence that REα promotes proliferation, while REβ activation induces protection against the mentioned diseases. However, in advanced stages of prostate cancer, the presence of REβ in prostate cells is associated with increased cell proliferation and increased patient mortality. It is likely that in this case REβ activate signaling pathways that promote androgen-independent proliferation, which would be important in the lack of response to androgen deprivation therapy frequently observed in PCa. REβ another important aspect is the regulation of the ERβ expression. This process is known to involve steroid hormones, but on the other hand, prolactin, a protein pituitary hormone, is also involved in both physiological and pathophysiological contexts. The knowledge of the normal and pathological mechanisms through the estrogens and its β receptors and prolactin regulate the prostate will contribute to the development of strategies for the treatment and prevention of BPH and PCa.
Key words: Estrogens; estrogen receptors; prostate; prostate cancer; prolactin.
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