RESUMO
The estrogen-estrogen receptor (ER) signaling pathway plays crucial physiologic roles in not only the control of reproduction, but also in the generation of cancer in the breast and uterus. While some ER target genes have been identified containing the estrogen-responsive element (ERE), others are activated eventually by ER via protein-protein interaction without binding to ERE. In a previous study, we identified that the proliferative phase-specific expression of the bcl-2 gene in glandular cells could be regulated by the binding of c-Jun to its motifs in the promoter. Results from our present study indicate that the menstrual cyclic expression of bcl-2 could be controlled by either direct binding of ERα to ERE in the c-Jun promoter or the interaction of ERα with c-Jun that binds to its motifs in the bcl-2 gene. Intriguingly, the transcriptionally active form of c-Jun phosphorylated at Ser63 was identified binding to its motifs in the bcl-2 gene in a menstrual cyclic non-specific manner. Our study revealed a novel mechanism that transcriptionally regulates the expression of bcl-2 in the normal human endometrium.
Assuntos
Endométrio/metabolismo , Receptor alfa de Estrogênio/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Adulto , Feminino , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Ciclo Menstrual , Pessoa de Meia-Idade , Fosforilação , Regiões Promotoras Genéticas/genética , Ligação Proteica , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-jun/genética , Serina/genética , Serina/metabolismo , Transcrição GênicaRESUMO
This study was carried out to evaluate the clinical efficacy of Xiong-gui-jiao-ai-tang (Kyuki-kyogai-to), a traditional Chinese herbal medicine, in the treatment of threatened abortion in early pregnancy. We enrolled 72 women diagnosed with threatened abortion at Osaka Medical College Hospital and assigned them at random to the following two groups: a group of 36 women who received Xiong-gui-jiao-ai-tang at a dose of 7.5 g/day and another group of 36 women who received human chorionic gonadotropin (hCG)(control group). We found that in the Xiong-gui-jiao-ai-tang group (2.9 + or - 3.5 days), the number of days required before hemostasis was reached in the uterus was significantly shorter than in the control group (10.8 + or - 8.2 days, p < 0.0001). Furthermore, the number of days required for retroplacental hematoma in the vicinity of the gestational sac to disappear was significantly shorter in the Xiong-gui-jiao-ai-tang group (9.9 + or - 7.1 days) than in the control group (23.2 + or - 12.8 days) (p < 0.0001). In retroplacental hematoma size, significant rates of reduction were obtained in both major and minor axis measurements at the 7th day of treatment for the Xiong-gui-jiao-ai-tang group compared to the control group (control vs Xiong-gui-jiao-ai-tang: major axis: 7.5 + or - 3.8% vs 42.3 + or - 10.5%; minor axis: 15.3 + or - 16.8% vs 71.5 + or - 48.2%)(p < 0.0001, each case). The results of this study demonstrated the beneficial effects of Xiong-gui-jiao-ai-tang in stabilizing early pregnancy. Xiong-gui-jiao-ai-tang can be expected to improve unstable early pregnancy with uterine bleeding and to prevent abortion.