In rodents, ovarian steroid hormones deeply influence the uterus during the estrous cycle, receptivity period, and implantation by triggering the expression of different sets of genes important for these processes. Since acrogranin (Grn), a growth factor present in many tissues, is expressed particularly highly in the uterus and the trophectoderm of mouse preimplantation embryos, our objective was determine whether steroids regulate Grn in a stage-specific manner. Prospective experimental laboratory study, using an in-vivo mouse model with physiologic and pharmacological treatments. The levels of acrogranin mRNA and protein were examined in the uteri of immature and adult mice following hormonal physiologic (estrous cycle) and pharmacological treatments (in oophorectomized animals) using in-situ hybridization, real time RT-PCR, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblotting, and immunohistochemistry. Acrogranin mRNA and protein expression progressively increased in the uteri from immature (young pups) to adult sexually mature animals. A recurrent, variable pattern of Grn gene and protein expression was determined to occur during the estrous cycle with particularly high levels at diestrus. The uteri of ovariectomized adult mice displayed a dose-dependent and additive acrogranin expression pattern in response to estradiol alone, progesterone, and estradiol plus rogesterone together. The blockage of progesterone and estrogen receptors with RU-486 and ICI 182,780, respectively, in ovariectomized animals followed by progesterone and estrogen stimulation resulted in a decreased Grn mRNA and protein expression when compared with the controls treated with a placebo. These findings indicate that Grn is a mediator of steroid action in the mouse uterus in vivo. However, low levels of Grn mRNA and protein were found in the uteri of young pups and gonadectomized animals without any hormonal stimulus whatsoever, suggesting that a small part of acrogranin gene expression is gonadal steroid hormone independent. Two important and interesting implications derived from these results are (1) the robustness of Grn expression during the diestrous stage and implantation window coupled with its crucial role during blastocyst development, indicate that acrogranin may be important for embryo receptivity and implantation and (2) the identification of acrogranin as a mediator of ovarian steroid action in uterus, along with its characteristics as a regulator of tumor growth and invasiveness, place it as a strong candidate for a gene involved in common uterine hormone-dependent pathologies like fibroids and endometrial cancer.