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Transcriptomic effects of progesterone and mifepristone in the cycling endometrium

ABSTRACT: Mifepristone is an antagonist of the progesterone receptor in clinical use. Here, we explored the effects of mifepristone alone, and the effect of progesterone after the dose of mifepristone, on the transcriptomic signature in endometria from cycling women.

ORGANISM(S): Homo sapiens

PROVIDER: GSE263868 | GEO | 2025/03/09

REPOSITORIES: GEO

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Transcriptomic effects of progesterone and mifepristone in the cycling endometrium

Project description:Transcriptomic effects of progesterone and mifepristone in the cycling endometrium

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Effects of high concentrations of progesterone and Mifepristone: a gene expression study of endometrial cancer cells

Project description:Patients with endometrial hyperplasia representing preliminary stages of endometrial cancer have shown to respond to therapy in 100% of the cases when treated with levonorgestrel -impregnated intrauterine device. Antiproliferative effect has also been reported after application of an anti-progestin impregnated intrauterine device which showed to induce endometrial atrophy. The intention of the present study was to obtain more information of novel therapeutic targets for hormonal treatment in endometrial hyperplasia and endometrial cancers. Gene expression of signaling pathways after stimulation of Ishikawa cells with high doses of progesterone (10 Î¼M) or Mifepristone (10 Î¼M) was performed. After using an oligo microarrays representing 24,650 human genes and 37,580 gene transcripts, 6,154 genes remained after pre-processing and filtering. This resulted in a total of 993 up-regulated genes with 189 genes for progesterone and 255 genes for Mifepristone. The 550 down regulated genes were distributed with 256 genes for progesterone, 127 genes for RU 486. The results showed that genes presenting the epidermal growth factor (EGF)/MAP-kinase pathway were significantly over-represented by progesterone treatment, whereas, by Mifepristone treatment genes involved in the p53 pathway were also up-regulated (data not shown). These genes may be interesting as potential new therapeutic targets in endometrial hyperplasia and endometrial cancer, as candidate genes for therapy response or as candidate markers for tumor progression. 20 samples, 4 different condition groups with 5 replicates for each group, linear factorial experimental design. Short time (4hrs) dose response to progesterone and Mifepristone in combination and alone. Only 18 samples are represented in this Series.

2010-05-06 | E-GEOD-14713 | biostudies-arrayexpress

Effects of high concentrations of progesterone and Mifepristone: a gene expression study of endometrial cancer cells

Project description:Patients with endometrial hyperplasia representing preliminary stages of endometrial cancer have shown to respond to therapy in 100% of the cases when treated with levonorgestrel -impregnated intrauterine device. Antiproliferative effect has also been reported after application of an anti-progestin impregnated intrauterine device which showed to induce endometrial atrophy. The intention of the present study was to obtain more information of novel therapeutic targets for hormonal treatment in endometrial hyperplasia and endometrial cancers. Gene expression of signaling pathways after stimulation of Ishikawa cells with high doses of progesterone (10 μM) or Mifepristone (10 μM) was performed. After using an oligo microarrays representing 24,650 human genes and 37,580 gene transcripts, 6,154 genes remained after pre-processing and filtering. This resulted in a total of 993 up-regulated genes with 189 genes for progesterone and 255 genes for Mifepristone. The 550 down regulated genes were distributed with 256 genes for progesterone, 127 genes for RU 486. The results showed that genes presenting the epidermal growth factor (EGF)/MAP-kinase pathway were significantly over-represented by progesterone treatment, whereas, by Mifepristone treatment genes involved in the p53 pathway were also up-regulated (data not shown). These genes may be interesting as potential new therapeutic targets in endometrial hyperplasia and endometrial cancer, as candidate genes for therapy response or as candidate markers for tumor progression.

2009-02-05 | GSE14713 | GEO

Comparison of the in vivo transcriptome of the myometrium exposed to mifepristone vs vehicle

Project description:Circulating progesterone (P4) levels decline before the onset of parturition in most animals, but not in humans. This has led to the suggestion that there is functional withdrawal of P4 action at the myometrial level prior to labor onset. However, to date, no evidence of a loss of P4 function has been provided. Mifepristone is a mixed progesterone and glucocorticoid receptor antagonist that is frequently used to induce human labor. However, its effect on the myometrial tissue transcriptome hs not been determined. In this study, we aimed to identify the effects of mifepristone treatment on the pregnant myometrium at term in order to better understand the possible mechanisms underlying the loss of P4 function in human labor.

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Project description:Progesterone receptor antagonism is gaining attention due to progesterone's recognized role as a major mitogen in breast tissue. Limited but promising data suggest the potential efficacy of antiprogestins in breast cancer prevention. The present study presents secondary outcomes from a randomized controlled trial examining changes in breast mRNA expression following mifepristone treatment in healthy women. We analyzed 32 paired breast biopsies from 16 healthy premenopausal women at baseline and after two months of mifepristone treatment. In total, twenty-seven differentially expressed genes were identified, with enriched biological functions related to extracellular matrix remodeling. Notably, the altered gene signature induced by mifepristone in vivo was rather similar to the in vitro signature. Furthermore, this expression gene signature was associated with breast carcinogenesis and significantly correlated with progesterone receptor expression status in breast cancer, as validated in The Cancer Genome Atlas dataset using the R2 platform. The present study is the first to explore the breast transciptome following mifepristone treatment in healthy breast tissue in vivo, enhancing the understanding of progesterone receptor modulator and its potential protective effects against breast cancer by investigating its action in healthy breast tissue.

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Progesterone-mediated gene expression in the human endometrial stromal compartment during the implantation window

Project description:Progesterone regulated genes in the endometrial stromal compartment were studied in proven fertile women using laser dissection capture microscopy followed by microarray. Endometrial biopsies were obtained from women before (control group, n=9) and after (study group, n=9) treatment with mifepristone. Stromal cells were isolated by Laser-capture microdissection and RNA was extracted. The gene expression was analyzed by microarray and reconfirmed by real-time PCR.

2014-07-16 | E-GEOD-59447 | biostudies-arrayexpress

Beneficial effects of mifepristone treatment in breast cancer patients selected by the progesterone receptor isoform ratio: Results from the MIPRA trial

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2022-10-17 | GSE212690 | GEO

Molecular characterization of PRM associated endometrial changes, PAEC, following mifepristone treatment.

Project description:The molecules significantly altered in endometrium displaying PAEC after three months of mifepristone exposure are mainly involved in the structural architecture of tissue, which may explain the morphological features of PAEC Our study has generated new knowledge on the molecular profile of endometrium displaying PAEC after 3 months of mifepristone treatment due to symptomatic leiomyoma. This knowledge is of great importance as the application of progesterone receptor modulators (PRMs) for the medical management of benign gynecological conditions is increasing.

2018-12-01 | GSE110232 | GEO

Transcription profiling of human endometrium from patients with a history of endometriosis vs. normal controls sampled at a range of menstrual cycle timepoints reveals progesterone resistance and candidate susceptibility genes in women with endometriosis

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2008-04-09 | E-GEOD-6364 | biostudies-arrayexpress

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