Estradiol-17β Upregulates Pyruvate Kinase M2 Expression to Coactivate Estrogen Receptor-α and to Integrate Metabolic Reprogramming With the Mitogenic Response in Endometrial Cells

Salama, Salama A.; Mohammad, Mahmoud A.; Diaz-Arrastia, Concepcion; Kamel, Marwa; Kılıç, Gökhan; Ndofor, Bih T.; AbdelBaki, Mohamed S.; Theiler, Stefan

doi:10.1210/jc.2013-2639

Cited by 30 publications

(12 citation statements)

References 59 publications

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“…Thus we propose that mouse decidualizing cells are eventually adapted to aerobic glycolysis due to Hif1␣ activation under progesterone priming. Similarly, in primary human endometrial stromal cells, estrogen has been proved to evoke a Warburg-like glucose metabolism by inducing dimeric Pkm2 (40).…”

Section: Discussionmentioning

confidence: 97%

Warburg-like Glycolysis and Lactate Shuttle in Mouse Decidua during Early Pregnancy

Zuo

et al. 2015

Journal of Biological Chemistry

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Background: Carbohydrate metabolism during decidualization is unknown. Results: Decidual cells undergo glycolysis upon progesterone signals, and the undifferentiated stromal cells consume lactate for proliferation. Inhibition of glycolysis or lactate flux could compromise decidual development. Conclusion: Warburg-like glycolysis and lactate communication play critical roles during decidualization. Significance: Our study will be valuable for understanding the mechanism underlying decidualization.

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Section: Discussionmentioning

confidence: 97%

Warburg-like Glycolysis and Lactate Shuttle in Mouse Decidua during Early Pregnancy

Zuo

et al. 2015

Journal of Biological Chemistry

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“…Other steroid hormones also coordinate both transcription and splicing decisions 29 . The thyroid hormone receptor (TR) is known to play a role in coordinating the regulation of transcription and alternative splicing 27 , and the oestrogen receptor (ER) can both regulate alternative promoter selection and induce alternative splicing of specific gene sets that can influence breast cancer cell behaviour 28 , 33 – 35 .…”

Section: Introductionmentioning

confidence: 99%

Androgen-dependent alternative mRNA isoform expression in prostate cancer cells

et al. 2018

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Background: Androgen steroid hormones are key drivers of prostate cancer. Previous work has shown that androgens can drive the expression of alternative mRNA isoforms as well as transcriptional changes in prostate cancer cells. Yet to what extent androgens control alternative mRNA isoforms and how these are expressed and differentially regulated in prostate tumours is unknown. Methods: Here we have used RNA-Seq data to globally identify alternative mRNA isoform expression under androgen control in prostate cancer cells, and profiled the expression of these mRNA isoforms in clinical tissue. Results: Our data indicate androgens primarily switch mRNA isoforms through alternative promoter selection. We detected 73 androgen regulated alternative transcription events, including utilisation of 56 androgen-dependent alternative promoters, 13 androgen-regulated alternative splicing events, and selection of 4 androgen-regulated alternative 3′ mRNA ends. 64 of these events are novel to this study, and 26 involve previously unannotated isoforms. We validated androgen dependent regulation of 17 alternative isoforms by quantitative PCR in an independent sample set. Some of the identified mRNA isoforms are in genes already implicated in prostate cancer (including LIG4, FDFT1 and RELAXIN), or in genes important in other cancers (e.g. NUP93 and MAT2A). Importantly, analysis of transcriptome data from 497 tumour samples in the TGCA prostate adenocarcinoma (PRAD) cohort identified 13 mRNA isoforms (including TPD52, TACC2 and NDUFV3) that are differentially regulated in localised prostate cancer relative to normal tissue, and 3 ( OSBPL1A, CLK3 and TSC22D3) which change significantly with Gleason grade and tumour stage. Conclusions: Our findings dramatically increase the number of known androgen regulated isoforms in prostate cancer, and indicate a highly complex response to androgens in prostate cancer cells that could be clinically important.

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“…The effects of estrogens on metabolic changes in pulmonary vasculature are unknown. Nonetheless, E2, via ERα-mediated upregulation of glycolytic enzymes, not only stimulates pathologic angiogenesis in breast cancer [186], but also boosts a mitogenic response in highly proliferative human endometrial cells and umbilical vein endothelial cells [187,188]. In contrast, because 2ME is a strong HIF-1α inhibitor, 2ME would be expected to inhibit metabolic reprograming in PAH.…”

Section: Me Hif-1α and Metabolic Reprograming In Pahmentioning

confidence: 99%

Estradiol Metabolism: Crossroads in Pulmonary Arterial Hypertension

Tofovic

Jackson

2019

IJMS

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Pulmonary arterial hypertension (PAH) is a debilitating and progressive disease that predominantly develops in women. Over the past 15 years, cumulating evidence has pointed toward dysregulated metabolism of sex hormones in animal models and patients with PAH. 17β-estradiol (E2) is metabolized at positions C2, C4, and C16, which leads to the formation of metabolites with different biological/estrogenic activity. Since the first report that 2-methoxyestradiol, a major non-estrogenic metabolite of E2, attenuates the development and progression of experimental pulmonary hypertension (PH), it has become increasingly clear that E2, E2 precursors, and E2 metabolites exhibit both protective and detrimental effects in PH. Furthermore, both experimental and clinical data suggest that E2 has divergent effects in the pulmonary vasculature versus right ventricle (estrogen paradox in PAH). The estrogen paradox is of significant clinical relevance for understanding the development, progression, and prognosis of PAH. This review updates experimental and clinical findings and provides insights into: (1) the potential impacts that pathways of estradiol metabolism (EMet) may have in PAH; (2) the beneficial and adverse effects of estrogens and their precursors/metabolites in experimental PH and human PAH; (3) the co-morbidities and pathological conditions that may alter EMet and influence the development/progression of PAH; (4) the relevance of the intracrinology of sex hormones to vascular remodeling in PAH; and (5) the advantages/disadvantages of different approaches to modulate EMet in PAH. Finally, we propose the three-tier-estrogen effects in PAH concept, which may offer reconciliation of the opposing effects of E2 in PAH and may provide a better understanding of the complex mechanisms by which EMet affects the pulmonary circulation–right ventricular interaction in PAH.

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Estradiol-17β Upregulates Pyruvate Kinase M2 Expression to Coactivate Estrogen Receptor-α and to Integrate Metabolic Reprogramming With the Mitogenic Response in Endometrial Cells

Cited by 30 publications

References 59 publications

Warburg-like Glycolysis and Lactate Shuttle in Mouse Decidua during Early Pregnancy

Warburg-like Glycolysis and Lactate Shuttle in Mouse Decidua during Early Pregnancy

Androgen-dependent alternative mRNA isoform expression in prostate cancer cells

Estradiol Metabolism: Crossroads in Pulmonary Arterial Hypertension

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