Expression of Angiotensin II Types 1 and 2 Receptors in Endometriotic Lesions

Abstract

Background/Aim: The aim of this study was to evaluate the gene and protein expression of angiotensin type (AT) 1, AT2 receptors in endometriotic lesions and its relation to prostaglandin (PG) synthases. Materials and Methods: Endometriosis samples were obtained from 32 patients with endometriotic cysts. Endometrial tissues were obtained during operations for benign gynecological conditions. The expression of the AT1 and AT2 receptor mRNA and that of PG-endoperoxide synthase 2 and microsomal PGE2 synthase-1 (mPGES-1) was examined by quantitative RT-PCR. Immunohistochemical staining was performed for these receptors. Results: AT1 and AT2 receptor proteins were mostly located in endometrial glandular epithelium and some stromal cells. Immunoreactivity of the receptor proteins was observed in both the eutopic endometrium and endometriotic lesions. The AT1/AT2 ratio in endometriotic cysts (median 7.29, range 1.88-187.60) was significantly increased compared with that in the eutopic endometrium in the proliferative-phase in controls (median 1.01, range 0.37-2.09, p < 0.001). There was a relationship between the AT1 mRNA expression and that of mPGES-1 mRNA in the endometriotic cysts (r = 0.394089, p < 0.05). There was a significant relationship between the mRNA expression of the AT2 receptor and that of mPGES-1 in eutopic endometrium of non-endometriotic control (r = 0.610714, p < 0.05). Conclusion: Renin-angiotensin system may play an important role in the pathophysiology of endometriosis.

The Expression of MAS1, an Angiotensin (1–7) Receptor, in the Eutopic Proliferative Endometria of Endometriosis Patients

“…We have demonstrated that both AT1 and AT2 receptors are expressed in endometriosis and the ratio of the AT1/AT2 mRNA levels is increased in an endometriosis-specific manner [13], suggesting that the AT1 pathway contributes to the pathogenesis of endometriosis at ectopic sites [13,14]. In this study, we focused on the MAS1 pathway in the endometria of endometriosis patients.…”

“…The details of the immunohistochemical staining are described in previous reports [13,16]. For MAS1 localization, we used a rabbit polyclonal antibody to MAS1 (ab66030, Abcam Inc., MA, USA) (at a 1: 100 dilution) for 1 h at room temperature.…”

“…Human renal tissue was used as the positive control, and the primary antibody was substituted with Rabbit Polyclonal Isotype Ctrl (Biolegend, Tokyo, Japan) for the negative controls. Immunoreactivity was scored as 3 for a strongly reactive stain, 1 for a weakly reactive but specific stain, 2 for a stain that was between 1 and 3, and 0 for a stain with no reactivity, as previously described [13,16,17,18].…”

“…RNA extraction, RT, and real-time qPCR were performed as described previously [13,16]. Total RNA was isolated from specimens with a TRIzol reagent (Invitrogen, Carlsbad, CA, USA) and stored at -80 ° C. The optical density ratios (260 nm/280 nm) of the RNA preparations were > 1.8.…”

“…Amplification was performed under the following conditions: 95 ° C for 3 minutes (holding stage), followed by 45 cycles of 95 ° C for 15 s and 60 ° C for 60 s. All assays were performed in triplicate. The AT1 and AT2 receptors primer sequences were described previously [13]. The primer sequences of MAS1 and β-actin [19] were described in Table 3.…”