We have previously shown that E2 and P4 have clear and distinct effects on inflammatory response and gastric epithelial changes during early H. pylori infection. Recently, Ohtani et al., have shown a protective role of E2 administration in H. pylori-infected InGas mice. Other studies have demonstrated that E2 and P4 have anti-ulcerative effects in murine gastric mucosa. ER and PR have been reported in human, mouse and rat stomach. However, there is no information to date of their expression and regulation in Mongolian gerbil stomach.
Ovariectomized adult female gerbils were subcutaneously treated with E2, and E2+P4. Uteri and stomachs were removed, the latter were cut along the greater curvature, and antrum and corpus were excised. Proteins were immunoblotted using antibodies that recognize ER-alpha, ER-beta, and PR-A and PR-B receptor isoforms. Tissues from rats treated in the same way were used as control.
Specific bands were detected for ER-alpha (68 kDa), and PR isoforms (85 and 120 kDa for PR-A and PR-B isoforms, respectively) in uteri, gastric antrum and corpus. We could not detect ER-beta isoform. PR isoforms were not regulated by E2 or P4 in uterus and gastric tissues of gerbils. ER-alpha isoform content was significantly down-regulated by E2 in the corpus, but not affected by hormones in uterus and gastric antrum. We have detected ER-alpha and both PR isoforms in gerbil gastric antrum and corpus. In the antrum, none of the receptors was regulated by E2 and P4, but in gastric corpus we observed a down-regulation by E2. Thus, our results show that ER-alpha regulation also depends on the type of cells present in the mucosa. The mechanisms involved in the lack of regulation of PR in gerbil stomach, as well as the differential regulation of ER-alpha by E2 deserve further research. The presence of ER-alpha and PR isoforms in gerbil stomach suggests that E2 and P4 actions in this organ are in part mediated by their nuclear receptors.
A research article to be published on October 7,2008 in the World Journal of Gastroenterology addresses this question. The research team led by Dr. Camacho-Arroyo from Universidad Nacional Autónoma de México used commercially available antibodies to detect estrogen and progesterone receptors isoforms in female gerbil stomach. They also evaluated the effects of E2 and E2+P4 in the regulation of these receptors. As it has been previously reported that stomach has steroidogenic activity, and that both estradiol (E2) and progesterone (P4) play differential roles in response to gastric injury and H. pylori infection, it was important to be able to detect these proteins in Mongolian gerbils stomach.
Specific bands for estrogen receptor (ER)-alpha (68 kDa), progesterone receptor (PR)-A (85 kDa) and PR-B (120 kDa) were detected, unfortunately they were unable to detect ER-beta isoform. The identity of the receptors was defined by using rat uteri samples along with the Mongolian gerbil uteri. This is important because Mongolian gerbils sex steroid receptors have not been sequenced at the gene or protein levels. The detection of these receptors with antibodies raised against other specie receptors suggests high conservation of the specific epitopes among species. The validation of commercially available antibodies for ER and PR in Mongolian gerbils adds applicability to the results of this study.
The regulation of ER and PR by E2 and P4 was first defined in target organs in the reproductive tract, and after several studies, there is enough evidence that this regulation is tissue specific and it is associated to the function of E2 and P4 in every particular tissue. ER and PR expression regulation in Mongolian gerbils has not been reported previously. The lack of regulation of ER and PR in gerbil uteri deserved further investigation. The differential regulation in gastric antrum and corpus suggests differential roles of these receptors in the different gastric mucosa. This study raises interesting questions to be addressed in future research.