Expression of ATF4 and Its regulation by steroid hormones in the mouse uterus during estrous cycle and peri-implantation Period

Abstract

Activating transcription factor (ATF) is a ubiquitous basic leucine zipper transcription factor that is a member of the ATF/CREB protein family. ATF4 is expressed in a wide variety of organs and regulate cell proliferation and differentiation. To investigate the expression of ATF4 and the effects of ovarian steroids on ATF4 gene expression in uterus, the changes in ATF4 expression during estrous cycles and peri-implantation period was examined in mice. The regulation of ATF4 expression by steroids was examined following the combinatorial treatment of 17β-estradiol (E2; 0.3 ㎍/head) and progesterone (P4; 1 ㎎/head) in ovariectomized (OVX) uterus. Mice were given steroids 2 weeks after OVX and killed at 6, 12, and 24 h after last steroid injection. On the other hand, uteri were sampled on days 1, 3, 4.5, and 6 of pregnancy. Quantitative RT-PCR showed that ATF4 mRNA was highly expressed in estrus-stage. In OVX mice ATF4 mRNA was up-regulated by E2 but attenuated by P4. In the pregnant uterus ATF4 mRNA was lower than that of estrus-stage uterus. These results suggest that ATF4 is regulated by estrogen and possibly involved in the control of endometrial proliferation in mouse uterus.