Progestin activation of nongenomic pathways via cross talk of progesterone receptor with estrogen receptor β induces proliferation of endometrial stromal cells

• Autores: Vallejo, G.; Ballaré, C.; Barañao, J.L.; Beato, M.; Saragüeta, P.
• Año de publicación: 2005
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Mol. Endocrinol. 2005;19(12):3023-3037
• Materia: estradiol; estrogen receptor beta; fulvestrant; gestagen; mifepristone; mitogen activated protein kinase 1; mitogen activated protein kinase 3; progesterone receptor; promegestone; animal cell; article; cell differentiation; cell nucleus membrane; cell proliferation; controlled study; decidualization; endometrium cell; enzyme activation; estrogen activity; female; hormonal regulation; immunoprecipitation; nonhuman; priority journal; progesterone release; protein cross linking; protein localization; rat; reporter gene; signal transduction; stroma cell; uterine cervix ripening; Active Transport, Cell Nucleus; Animals; Cell Nucleus; Cell Proliferation; Cytoplasm; Endometrium; Enzyme Activation; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Genes, Reporter; Genome; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mutation; Progestins; Promegestone; Proto-Oncogene Proteins c-akt; Rats; Receptors, Progesterone; Signal Transduction; Stromal Cells; Trans-Activation (Genetics); Transcription, Genetic; Animalia
• Institución: Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales

Uterine decidualization is characterized by stromal cell proliferation and differentiation, which are controlled by ovarian hormones estradiol and progesterone. Here we report that the proliferative response of UIII rat uterine stromal cells to a short treatment with progestins requires active progesterone receptor (PR) and estrogen receptor β (ERβ) as well as a rapid and transient activation of Erk1-2 and Akt signaling. The optimal R5020 concentration for the proliferative response as well as for activation of the signaling cascades was between 10 and 100 pM. UIII cells are negative for ERα and have low levels of ERβ and PR located mainly in the cytoplasm. Upon progestin treatment PR translocated to the cell nucleus where it colocalized with activated Erk1-2. Neither progestins nor estradiol transactivated the corresponding transfected reporter genes, suggesting that endogenous PR and ERβ are transcriptionally incompetent. A fraction of endogenous PR and ERβ form a complex as demonstrated by coimmunoprecipitation. Taken together, our results suggest that the proliferative response of uterine stromal cells to picomolar concentrations of progestins does not require direct transcriptional effects and is mediated by activation of the Erk1-2 and Akt signaling pathways via cross talk between PR and ERβ. Copyright © 2005 by The Endocrine Society.
Fil:Vallejo, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Ballaré, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Barañao, J.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Saragüeta, P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.