Estrogen receptors mediate rapid activation of phospholipase C pathwayin the rat endometrium

ABSTRACT

The aim of the present study was to investigate the activation of rapid signaling events by 17b-estradiolin the rat uterus. 17b-Estradiol induced a rapid increase of total [3H]-inositol phosphate accumulation inthe whole uterus and endometrium, but not in the myometrium. The effect of 17b-estradiol in the endometriumwas blocked by phospholipase C (PLC) inhibitor (U73122), estrogen receptors antagonist (ICI 182,780), exportin CRM1 inhibitor (leptomycin B) and selective inhibitor of the SRC family of protein tyrosine kinases (PP2). Furthermore, a selective agonist of ESR1 (PPT) and a selective agonist of GPER (G-1) also induced a rapid increase of total [3H]-inositol phosphate accumulation in the endometrium.The G-1 effects were blocked by GPER antagonist (G-15). 17b-Estradiol and G-1 promoted an additive effect on total [3H]-inositol phosphate accumulation. In conclusion, the present results indicate that a rapid activation of the PLC-mediated phosphoinositide hydrolysis occurred in the rat endometrium after 17b-estradiol stimulation, and this effect was mediated by ESR1 that underwent nuclear export after hormonestimulation, and that GPER activation may play an additive role for this response. These rapid actions might be one of the key steps that mediate the estrogen-dependent activation of cellular events in the endometrium.