Ic endometrial epithelium (Figure 3G and H). ER was strongly localized
Ic endometrial epithelium (Figure 3G and H). ER was strongly localized to the glandular epithelium and stromal cells in the eutopic RG7800 site endometrium (Figure 3I) and faintly localized in the control ectopic endometrium (Figure 3J). Dienogest and LA treatment had no effect on the ER expression (Figure 3K and L). ER immunoreactivity appeared faintly in the eutopic endometrial samples (Figure 3M). In contrast, ER was strongly localized to the epithelium and stromal cells in the ectopic endometrium (Figure 3N). Although dienogest treatment decreased the ER expression in ectopic endometrioma (Figure 3O), LAtreatment seemed to have no effect on the ER expression (Figure 3P). No immunostaining was found in eutopic or ectopic endometrium when the primary antibodies were omitted (data not shown).Discussion The current study demonstrated statistically significant decreases in both PR and PR-A messenger RNA and proteins in ectopic endometrium derived from females with endometrioma who did not receive any medical treatment (Figure 1A, 1B, 3B, and 3F). Furthermore, the relative expressions of PR-B and PR-A were significantly lower in ectopic endometrium (Figure 1C). According to Attia et al. [20], the resistance of endometriotic tissue to progesterone, evident in both laboratory and clinical observations, can be explained by the absence of PR-B transcripts and proteins and the presence of PR-A in ectopic lesions. Similar findings have been reported in epithelial cells selected from aDienogest LAPEControlAPR-ABCDEPR-BFGHIER-JKLMER-NOPFigure 3 Typical example of PR and ER isoform expression in patients with ovarian endometriosis. PR-A and PR-B were detected using PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26795252 PR-A (A, B, S, D) and PR-B (E, F, G, H) antibodies. ER and ER were detected using ER (I, J, K, L) and ER (M, N, O, P) antibodies. The eutopic endometrium (A, E, I, M) in the proliferative phase was obtained from females undergoing hysterectomy for uterine fibroids. The ectopic endometrium was obtained from endometrioma of the control females (B, F, J, N), dienogest-treated females (C, G, K, O) and LA-treated females (D, H, L, P). Scale bar: 25 m.Hayashi et al. Journal of Ovarian Research 2012, 5:31 http://www.ovarianresearch.com/content/5/1/Page 7 ofsmall number of ectopic samples [10]. Recently, independent investigators suggested that alterations in the relative expressions of PR-A and PR-B in endometrial cells may also play a pivotal role in the pathogenesis of endometriosis. A decreased PR-B/PR-A ratio has been demonstrated PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27663262 in ectopic tissue [5,10], and our findings are consistent with the results of these studies. Several investigators have reported markedly higher levels of ER and lower levels of ER in human endometriotic tissues and primary stromal cells compared with that observed in eutopic endometrial tissues and cells [22,40]. Recently, Bulun [41] reported that the levels of the nuclear receptors ER, ER and PR are quite different in endometriotic tissue and endometrium. The high ER/ ER ratiosin endometriotic stromal cells in turn lead to increased ER binding to the PR promoter and mediate downregulation of the expression of PR [21]. ER acts as a suppressor of ER in both endometrial and endometriotic stromal cells by binding to regulatory elements of specific promoters of the ER and PR genes [42]. Therefore, ER deficiency in endometriotic patients may be responsible for the failure of E2 to induce the PR expression, thus contributing to secondary PR deficiency and progesterone resistance.
