Corpora Cavernosa Estrogen Receptor Beta On The The Role And Mechanism Of Erectile Dysfunction

Objective:Endothelial dysfunction is one of the pathological basis of ED. Estrogen has a protective effect on the cardiovascular endothelial through its receptors. Estrogen receptor has two isoforms including a and β, and in the penile corpus cavernosum, most of them is ERβ. This study was to investigate the protective effect of ERβ on penile vascular endothelial in mice, and observe the expression changes of eNOS-NO pathway, and determine the molecular mechanisms by which ER(3protects corpus cavernosum vascular endothelial system.Methods:We selected randomly12ERβKO and12C57BL/6male mice, and divided them into four groups:normal control, ERβKO, ERβKO+TNFa, and wild-type+TNFa group. The former two were treated with saline, while the latter two by intraperitoneal injection of TNFa6μg/kg·d for14days.Then we observed the spontaneous erectile response induced by APO and changes of the endothelial cells by immunohistochemistry staining of CD34and vWF, and detected cell apoptosis in penile cavernous tissue by TUNEL. We also detect the mice corpus cavernosum tissue structure with Masson and HE staining.And then we extracted the total mRNA from mice penis, using RT-PCR technique to detect the mRNA expression of relevant molecules in eNOS-NO pathway, such as eNOS, caveolin-1and Cam, and extracted the total protein in mice penile tissue to detect the protein expression of relevant molecules by Western blotting, and we observed the changes of eNOS by immunohistochemistry staining.Results:The results of APO showed that, compared with the normal control group, the ERβKO group significantly increased erectile latency (P＜0.05), but no significant difference in the number of erections; the ERβKO+TNFa and wild-type-TNFa groups, too, exhibited remarkably longer erectile latency (P<0.05) but fewer erections (T＜0.05), with even more obvious changes in the ERβKO+TNFa group. The expressions of CD34and vWF were significantly reduced in ERPKO group (CD34:2.25±0.50, vWF:2.00±0.00), ERβKO+TNFa group (CD34:0.250.50, vWF:0.33±0.58) and wild-type+TNFa treated group (CD34:1.50±0.58, vWF:1.25±0.50) as compared with those in the control (CD34:3.00±0.00, vWF:2.75±0.50)(P＜0.05), even lower in the ERβKO+TNFa than in the wild-type+TNFa group(P <0.05). Apoptotic cells were found only in the ERβKO+TNFa group. The results of Masson and HE staining showed no obvious change under the microscope. The results of RT-PCR consistent with the Western blotting:compared with the normal control group, the expression of eNOS, Cam were decreased, but the caveolin-1was increased in the ERβKO group, the difference was statistically significant(p<0.05); after the administration of TNFa, compared with the wild-type+TNFa group, the expression of eNOS and Cam were decreased, but the caveolin-1was increased in the ERβKO group, the difference was statistically significant (P<0.05). Immunohistochemical results are consistent with the above.Conclusion:1. After knocking out ERβ, especially being treated with the endothelial injury factor of TNFa, the endothelial cells decreased in the penile vascular, indicate that ERβ may have a protective effect on the penile cavernous sinus endothelium.2. After the ERβ knockout, especially treated with the endothelial injury factor of TNFa, the expression of eNOS was reduced, and eNOS-NO pathway were down-regulated, suggesting that ERp has a protective effect on the penile cavernous sinus endothelium by the way of eNOS-NO pathway.