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Progestin Activation of Nongenomic Pathways via Cross Talk of Progesterone Receptor with Estrogen Receptor ß Induces Proliferation of Endometrial Stromal Cells

Instituto de Biología y Medicina Experimental (G.V., J.L.B., P.S.), Consejo Nacional de Investigaciones Científicas y Técnicas and Departamento de Química Biológica (J.L.B., P.S.), Facultad de Ciencias Exactas y Naturales Universidad de Buenos Aires, 1428 Buenos Aires, Argentina; and Centre de Regulació Genòmica (G.V., C.B., M.B.), Universitat Pompeu Fabra, 08003 Barcelona, Spain

Address all correspondence and requests for reprints to: Patricia Saragüeta, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Obligado 2490, (1428) Buenos Aires, Argentina. E-mail: sarag{at}dna.uba.ar.

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 ß (ERß) 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 ER and have low levels of ERß 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 ERß are transcriptionally incompetent. A fraction of endogenous PR and ERß 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 ERß.

NURSA Molecule Pages Link:

Nuclear Receptors:   ERα  |  ERβ  |  PR

Ligands:   17β-Estradiol  |  RU486  |  R5020

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