Steroid hormones, cytokines, and growth factors have a major role in evoking local endometrial changes needed for trophoblast implantation. In the present study, the effect of interleukin-1beta (IL-1beta), 17-beta estradiol (E2), and progesterone (Pr) on activin A and follistatin (FS) secretion from cultured human endometrial stromal cells (HESCs) is evaluated. HESCs were obtained from healthy human endometrial samples (n = 8) collected from healthy women. The cells were cultured and stimulated with E2 (10(-7) M, 10(-6)M), Pr (10(-7)M, 10(-6)M), IL-1beta (500 pg/mL), IL-1beta (500 pg/mL) + E2 (10(-6)M), and IL-1beta (500 pg/mL) + Pr (10(-6)M). Activin A and FS secretion and mRNA expression were assayed by enzyme-linked immunosorbent assay and semiquantitative reverse transcriptase-polymerase chain reaction, respectively. Pr (10(-7) M, 10(-6) M) significantly increased activin A secretion and mRNA expression from HESCs, but E2 did not show remarkable effects. The addition of IL-1beta (P< .001), IL- 1beta + E2 (P < .01), and IL-1beta + Pr (P< .001). significantly stimulated activin A secretion and mRNA expression, compared to untreated cells. Activin A expression and secretion after the coincubation of IL-1beta+ Pr were significantly higher than after IL-1betaand IL-1beta+ E2 stimuli ( P< .01 and P< .001, respectively). Neither Pr nor E2 and IL-1beta had a significant effect on FS secretion and expression. IL-1betaand Pr stimulated activin A but not FS secretion from cultured HESCs, and the effect of IL-1betawas augmented by Pr. These findings, together with the evidence that activin A is involved in trophoblast implantation, suggest the existence of a complex cross-talk by which the ovary, through Pr secretion, and the embryo, through IL-1beta production, may trigger the endometrial induction of activin A and consequently timing implantation.