P450Arom induction in isolated control endometrial cells by peritoneal fluid from women with endometriosis

Castro, J.; Torres, Marisa; Sovino, Hugo; Fuentes, Ariel; Boric, M A; Johnson, Marı́a Cecilia

doi:10.1016/j.fertnstert.2010.03.036

Cited by 8 publications

(7 citation statements)

References 56 publications

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“…The additive effect of E 2 and PGE 2 on P 450 Arom protein contents indicates different activation mechanisms. Similar additive effect we reported previously in isolated control epithelial cells treated with peritoneal fluid from endometriosis women (PF-E) and Bu 2 cAMP [ 44 ] mimicking the conditions of the endometriotic lesions. In our control epithelial cell model, P 450 Arom stimulation by E 2 was through ERα and GPER1, but not through ERβ as it was previously proposed [ 1 , 45 ] probably by the use of isolated control epithelial cells and not endometriotic stromal cells.…”

Section: Discussionsupporting

confidence: 88%

“…The non-classic receptor GPER1 mediating the E 2 stimulatory action on SF-1 protein content as shown by our G1 data, is in agreement with SF-1 activation and endometrial cell proliferation through the PI3K and MAPK pathways activated in several cell lines transfected with GPER1 [ 39 , 40 ]. However, cAMP pathway cannot be ruled out according to similar response to (Bu) 2 cAMP of control or SF-1-transfected endometrial epithelial cells as we previously reported [ 44 ].…”

Section: Discussionmentioning

confidence: 92%

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Differential expression of upstream stimulatory factor (USF) 2 variants in eutopic endometria from women with endometriosis: estradiol regulation

et al. 2015

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BackgroundEndometriosis, pro-inflammatory and invasive benign disease estrogen dependent, abnormally express in endometria the enzyme P450Arom, positively regulated by steroid factor-1 (SF-1). Our objective was to study the nuclear protein contents of upstream stimulating factor 2 (USF2a and USF2b), a positive regulator of SF-1, throughout the menstrual cycle in eutopic endometria from women with and without (control) endometriosis and the involvement of nuclear estrogen receptors (ER) and G-coupled protein estrogen receptor (GPER)-1.ResultsUpstream stimulating factor 2 protein contents were higher in mid (USF2b) and late (USF2a and USF2b) secretory phase in eutopic endometria from endometriosis than control (p < 0.05). In isolated control epithelial cells incubated with E2 and PGE2, to resemble the endometriosis condition, the data showed: (a) significant increase of USF2a and USF2b nuclear protein contents when treated with E2, PPT (specific agonist for ERα) or G1 (specific agonist for GPER1); (b) no increase in USF2 binding to SF-1 E-Box/DNA consensus sequence in E2-treated cells; (c) USF2 variants protein contents were not modified by PGE2; (d) SF-1 nuclear protein content was significantly higher than basal when treated with PGE2, E2 or G1, stimulation unaffected by ICI (nuclear ER antagonist); and (e) increased (p < 0.05) cytosolic protein contents of P450Arom when treated with PGE2, E2, PPT or G1 compared to basal, effect that was additive with E2 + PGE2 together. Nevertheless, in endometriosis cells, the high USF2, SF-1 and P450Arom protein contents in basal condition were unmodified.ConclusionThese data strongly suggest that USF2 variants and P450Arom are regulated by E2 through ERα and GPER1, whereas SF-1 through GPER1, visualized by the response of the cells obtained from control endometria, being unaffected the endogenously stimulated cells from endometriosis origin. The lack of E2 stimulation on USF2/SF-1 E-Box/DNA-sequence binding and the absence of PGE2 effect on USF2 variants opposite to the strong induction that they exert on SF1 and P450 proteins suggest different mechanisms and indirect regulations. The sustained USF2 variants protein expression during the secretory phase in eutopic endometria from women with endometriosis may participate in the pathophysiology of this disease strongly associated with infertility and its characteristic endometrial invasion to ectopic sites in the pelvic cavity.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 92%

Differential expression of upstream stimulatory factor (USF) 2 variants in eutopic endometria from women with endometriosis: estradiol regulation

et al. 2015

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“…Wang and colleagues also showed global downregulation in the circulating levels of miRNAs in the serum of women with endometriosis, with 91% of significantly differentiated miRNAs showing decreased expression in endometriosis patients [67]. There are very few studies that have measured miRNAs in the peritoneal fluid (PF), which is the most dynamic component and major player in the etiology of endometriosis [11], [68], [69].…”

Section: Introductionmentioning

confidence: 99%

Redox regulation of microRNAs in endometriosis-associated pain

2017

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Endometriosis is a chronic, painful condition with unknown etiology. A differential expression of microRNAs in the endometriotic tissues from women with endometriosis with pain compared to those without suggested a plausible role for miRNA or epigenetic mechanisms in the etiology of endometriotic pain. The peritoneal milieu is involved in maintenance of endometriotic lesion and nociception. We recently showed the mechanistic role for oxidized-lipoproteins (ox-LDLs) present in peritoneal fluid (PF) in endometriosis and pain. We explored the possibility of ox-LDLs modulating the expression of miRNAs in a manner similar to PF from women with endometriosis. Expression levels of miRNAs and their predicted nociceptive and inflammatory targets were determined in PF and ox-LDL treated human endometrial cell-lines. Samples from IRB-approved and consented patients with and without endometriosis or pain were used. These were compared to endometrial cell-lines treated with various forms of oxidized-lipoproteins. RNA (including miRNAs) were isolated from treated endometrial cells and expression levels were determined using commercial miRNome arrays. Cell lysates were used in immunoblotting for inflammatory proteins using a protein array. Twenty miRNAs including isoforms of miR-29, miR-181 and let-7 were mutually differentially expressed in cells treated with PF from endometriosis patients with pain and those treated with ox-LDL components. The ox-LDLs and endo-PF treatment also produced significant overexpression of microRNA predicted target genes nerve growth factor, interleukin-6 and prostaglandin E synthase and overexpression of their downstream protein targets Mip1α and MCP1. This study showed similarities between miRNA regulation in PF from endometriotic women and ox-LDLs present in abundance in the PF of these women. Key miRNAs responsible for targeting nociceptive and inflammatory molecules were downregulated in the presence of ox-LDLs and endo-PF, thus playing a role in the etiology of endometriotic pain. These redox-sensitive miRNAs can be of potential use as targets in the treatment of endometriosis-associated pain.

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“…Several studies report that protein and mRNA expression of P450arom can be detected in ectopic and/or eutopic endometrium of endometriosis patients, but not in normal endometrium (Noble et al 1996a, Kitawaki et al 1997, 1999, Tsai et al 2001, Dassen et al 2007, Hudelist et al 2007, Smuc et al 2007, Bukulmez et al 2008a, Attar et al 2009, Šmuc et al 2009, Morsch et al 2009, Huhtinen et al 2012b, 2014, Shen et al 2013, Suganuma et al 2014, Fouquet et al 2016 although this is disputed by others who failed to detect expression in either ectopic or eutopic endometrial tissue (Colette et al 2009, Delvoux et al 2009, 2014, others record expression in normal endometrium (Tseng 1984, Neulcn et al 1987, Huang et al 1989, Castro et al 2010 and in endometrium from women with and without endometriosis (Aghajanova et al 2009). Variations in the location of P450arom have also been recorded with detection in epithelial cells (Kitawaki et al 1997, Bukulmez et al 2008a, Castro et al 2010, but mostly in stromal cells (Noble et al 1996a, Zeitoun et al 1999, Suganuma et al 2014 (Supplementary Tables 3 and 4). Some of the variations in the reported patterns of expression may relate to use of different antibodies, recovery of eutopic endometrium at different stages of the cycle, the type of lesion or the status of the inflammatory microenvironment as discussed below.…”

Section: Aromatase (Cyp19)mentioning

confidence: 99%

SULFATION PATHWAYS: Contribution of intracrine oestrogens to the aetiology of endometriosis

Piccinato

Malvezzi

Gibson

et al. 2018

Journal of Molecular Endocrinology

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Endometriosis is an incurable hormone-dependent inflammatory disease that causes chronic pelvic pain and infertility characterized by implantation and growth of endometrial tissue outside the uterine cavity. Symptoms have a major impact on the quality of life of patients resulting in socioeconomic, physical and psychological burdens. Although the immune system and environmental factors may play a role in the aetiology of endometriosis, oestrogen dependency is still considered a hallmark of the disorder. The impact of oestrogens such as oestrone and particularly, oestradiol, on the endometrium or endometriotic lesions may be mediated by steroids originating from ovarian steroidogenesis or local intra-tissue production (intracrinology) dependent upon the expression and activity of enzymes that regulate oestrogen biosynthesis and metabolism. Two key pathways have been implicated: while there is contradictory data on the participation of the aromatase enzyme (encoded by ), there is increasing evidence that the steroid sulphatase pathway plays a role in both the aetiology and pathology of endometriosis. In this review, we consider the evidence related to the pathways leading to oestrogen accumulation in endometriotic lesions and how this might inform the development of new therapeutic strategies to treat endometriosis without causing the undesirable side effects of current regimes that suppress ovarian hormone production.

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P450Arom induction in isolated control endometrial cells by peritoneal fluid from women with endometriosis

Cited by 8 publications

References 56 publications

Differential expression of upstream stimulatory factor (USF) 2 variants in eutopic endometria from women with endometriosis: estradiol regulation

Differential expression of upstream stimulatory factor (USF) 2 variants in eutopic endometria from women with endometriosis: estradiol regulation

Redox regulation of microRNAs in endometriosis-associated pain

SULFATION PATHWAYS: Contribution of intracrine oestrogens to the aetiology of endometriosis

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