Transforming Growth Factor-β2 and Its Receptor Type II Messenger RNA Levels in Mice Endometrium and Their Regulation by Sex Steroids During Estrous Cycle

Despite increasing evidence pointing to the involvement of transforming growth factor-β superfamily in the regulation of reproduction, a definitive role of TGF-β2 and its receptor type II in the uterus is currently unclear. In this study, using semi-quantitative reverse transcriptase PCR (RT-PCR) and real-time PCR techniques (qPCR), TGF-β2 and its receptor type II (TGF-βRII) mRNA levels were examined in mouse endometrium during estrous cycle and in response to an acute exposure of 17β-estradiol (E2) and progesterone (P4). We found that TGF-βRII mRNA was expressed at a very low level during diestrus, and remained comparatively higher at proestrus, estrus and metestrus stages with no significant differences between them. On the contrary, the average TGF-β2 mRNA levels abruptly increased from estrus to diestrus stages and then briskly decreased at proestrus, the proliferative stage of the cycle. These results suggest that both TGF-β2 and its receptor type II are functional during proliferation as well as apoptosis of mice endometrial epithelial and stromal cells. A single injection of E2 or P4 at diestrus stage mice caused significant attenuation of the expression of TGF-β2 mRNA after 8 h of treatment compared to sesame oil control. Inhibition induced by P4 was comparatively stronger than that induced by E2 and results further showed that combined injection of E2 and P4 had similar inhibitory effects as that of P4 alone on TGF-β2 expression. In contrast, expression of TGF-βRII mRNA was not significantly altered by ovarian steroids administered either alone or in combination. Results further demonstrated that in short-term endometrial tissue incubation, p38 MAPK pathway was involved in the steroid-mediated inhibition of TGF-β2 mRNA with no effect on TGF-βRII mRNA. This result suggests that p38 MAPK pathway may be an important regulator of TGF-β2 and TGF-βRII mRNA expression in vitro in diestrus endometrium, in cooperation with ovarian steroids.