Differential effects of progesterone and medroxyprogesterone acetate on normal breast cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE23500 | GEO | 2011/05/30
SECONDARY ACCESSION(S): PRJNA131013
REPOSITORIES: GEO
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Project description:Comparison between the effects of progesterone (P4) and medroxyprogesterone acetate (MPA) combined to estradiol (E2) on gene expression in normal breast cells to provide insight on their possible different impact on breast cancer risk in vivo. Total RNA obtained from cultures of normal human breast epithelial cells (HBE) under E2, E2+MPA and E2+P4 six hour treatments, compared to untreated HBE cells
2011-05-30 | E-GEOD-23500 | biostudies-arrayexpress
Project description:Here we report the gene expression profile of in vitro cultured human endometrial stromal cells treated with siRNA targeting FOXO1 piror to eutherian differentiation media exposure. The eutherian differentiation media contains cyclic AMP (cAMP) analogue 8-Br-cAMP and the progesterone (P4) analogue medroxyprogesterone acetate (MPA).
2018-06-21 | GSE115832 | GEO
Project description:Medroxyprogesterone acetate (MPA) is a progestin that can bind to and activate progesterone, androgen and glucocorticoid receptors. However, it is not known which receptor mediates MPA action in a cellular context where all three of these receptors are co-expressed and functional. This microarray experiment was performed to compare the transcriptomes induced by MPA and the cognate ligands for these receptors ie progesterone (PROG), 5a-dihydrotestosterone (DHT) and dexamethasone (DEX) in breast cancer cells to determine which was most similar to MPA.
2020-01-22 | GSE139870 | GEO
Project description:Context: Progesterone is important physiologically and therapeutically to maintain uterine quiescence during pregnancy. It acts in part through controlling myometrial gene expression. Objective: To use expression microarray and qRT-PCR validation to determine the changes in gene expression induced by prolonged exposure to a synthetic progestogen. Design: Myometrial explants, obtained at elective Caesarean section (n=9 patients), were maintained in culture, under 0.6g tension, for 3 days in the presence or absence of medroxyprogesterone acetate (MPA, 100nM). Expression array was performed using Illumina human-8 v3 beadchip arrays. Approximately 30% of differentially expressed transcripts were validated in biological replicates (n=10) using qRT-PCR. Results: Transcripts from 114 genes were significantly differentially expressed. These were significantly enriched in inflammatory response (P=0.00001), growth factor activity (P=0.0004) and cytokine activity genes (P=0.008). 34 transcripts were validated using qRT-PCR using an additional independent sample set obtained from 10 further women. There was very close agreement in the fold changes obtained by array and qRT-PCR analysis (r2=0.9, P<0.0001). We confirmed significant down-regulation of a number of genes which have been well characterized as progesterone sensitive, such as IL1B, IL6, PTGS2 and GJA1. However, the top and 6th most down-regulated genes encoded two cytokines, IL11 and IL24, respectively, not previously implicated in mediating the effects of progesterone in myometrium. Both were validated by qRT-PCR (4.3-fold and 2.2-fold down-regulated, both P<0.001). Conclusions: Progestogens control expression of multiple genes in myometrium, including many with no previously recognised role, including IL11 and IL24. It is plausible that proteins encoded by some of these genes may have important, but as yet uncharacterized effects in controlling human parturition. 9 paired samples of human myometrium treated with MPA (10-7M) or vehicle
2011-06-08 | E-GEOD-22961 | biostudies-arrayexpress
Project description:Agilent 4x44k Whole Mouse Genome v1 Microarrays were used to analyze aortic transcriptome of mice substituted with medroxyprogesterone acetate, norethisterone acetate or placebo after having been ovariectomized. The aim of this experiment was to detect genes regulated in the gestagen-treated groups as compared to placebo that might be involved in thrombotic events Aortic gene expression was analyzed in ApoE-deficient mice after ovariectomy and 90 days of hormone- or placebo-treatment (medroxyprogesterone acetate or norethisterone acetate) and feeding a high-fat Western-type diet.
2014-06-30 | E-GEOD-57972 | biostudies-arrayexpress
Project description:Context: Progesterone is important physiologically and therapeutically to maintain uterine quiescence during pregnancy. It acts in part through controlling myometrial gene expression. Objective: To use expression microarray and qRT-PCR validation to determine the changes in gene expression induced by prolonged exposure to a synthetic progestogen. Design: Myometrial explants, obtained at elective Caesarean section (n=9 patients), were maintained in culture, under 0.6g tension, for 3 days in the presence or absence of medroxyprogesterone acetate (MPA, 100nM). Expression array was performed using Illumina human-8 v3 beadchip arrays. Approximately 30% of differentially expressed transcripts were validated in biological replicates (n=10) using qRT-PCR. Results: Transcripts from 114 genes were significantly differentially expressed. These were significantly enriched in inflammatory response (P=0.00001), growth factor activity (P=0.0004) and cytokine activity genes (P=0.008). 34 transcripts were validated using qRT-PCR using an additional independent sample set obtained from 10 further women. There was very close agreement in the fold changes obtained by array and qRT-PCR analysis (r2=0.9, P<0.0001). We confirmed significant down-regulation of a number of genes which have been well characterized as progesterone sensitive, such as IL1B, IL6, PTGS2 and GJA1. However, the top and 6th most down-regulated genes encoded two cytokines, IL11 and IL24, respectively, not previously implicated in mediating the effects of progesterone in myometrium. Both were validated by qRT-PCR (4.3-fold and 2.2-fold down-regulated, both P<0.001). Conclusions: Progestogens control expression of multiple genes in myometrium, including many with no previously recognised role, including IL11 and IL24. It is plausible that proteins encoded by some of these genes may have important, but as yet uncharacterized effects in controlling human parturition.
2011-06-08 | GSE22961 | GEO
Project description:Use of long-acting progestin-only contraceptives (LAPCs) offers a discrete and highly effective family planning method. Abnormal uterine bleeding (AUB) is the major side effect of, and cause for, discontinuation of LAPCs. The endometria of LAPC-treated women display abnormally enlarged, fragile blood vessels, decreased endometrial blood flow and oxidative stress. To understand the mechanisms underlying AUB, we propose to identify LAPC-modulated unique gene cluster(s) in human endometrial stromal cells (HESCs). Protein and RNA isolated from cultured HESCs treated 7 days with estradiol (E2) or E2+medroxyprogesterone acetate (MPA) or E2+ etonogestrel (ETO) or E2+progesterone (P4) were analyzed by q-PCR and immunoblotting. HSCORES were determined for immunostained-paired endometria of pre-and 3 months post-Depo-Provera (Depo) treated women (n=6) and ovariectomized guinea pigs (GPs; n=12) treated with placebo or E2 or MPA or E2+MPA for 21 days. In HESCs, whole genome analysis identified a 67-gene group regulated by all three progestins, whereas a 235-gene group was regulated by E2+ETO and E2+MPA, but not E2+P4. Ingenuity pathway analysis identified glucocorticoid receptor (GR) activation as an upstream regulator of the 235 LAPCMPA and ETO-specific genes. Among these, microarray results demonstrated significant enhancement of FKBP51, a repressor of PR/GR transcriptional activity, by both LAPCsMPA and ETO. q-PCR and immunoblot analysis confirmed the microarray results. In endometria of post-Depo versus pre-Depo administered women, FKBP51 expression was significantly increased in endometrial stromal and glandular cells. In GPs, E2+MPA or MPA significantly increased FKBP51 immunoreactivity in endometrial stromal and glandular cells versus placebo- and E2-administered groups. LAPC MPA or ETO administration activates GR signaling and increases endometrial FKBP51 expression, which could be one of the mechanisms causing AUB by inhibiting feeds back to inhibit PR- and GR-mediated transcription. The resultant PR- and/or GR-mediated functional withdrawal may contribute to associated endometrial inflammation, aberrant angiogenesis, and bleeding.
2015-08-14 | GSE72040 | GEO
Project description:The hormonal contraceptive medroxyprogesterone acetate (MPA) is associated with increased risk of human immunodeficiency virus (HIV), via incompletely understood mechanisms. Increased diversity in the vaginal microbiota modulates genital inflammation and is associated with increased HIV-1 acquisition. However, the effect of MPA on diversity of the vaginal microbiota is relatively unknown. In a cohort of female Kenyan sex workers, negative for sexually transmitted infections (STIs), with Nugent scores <7 (N=58 of 370 screened), MPA correlated with significantly increased diversity of the vaginal microbiota as assessed by 16S rRNA gene sequencing. MPA was also significantly associated with decreased levels of estrogen in the plasma, and low vaginal glycogen and α-amylase, factors implicated in vaginal colonization by lactobacilli, bacteria that are believed to protect against STIs. In a humanized mouse model, MPA treatment was associated with low serum estrogen, low glycogen and enhanced HIV-1 susceptibility. The mechanism by which the MPA mediated changes in the vaginal microbiota may contribute to HIV-1 susceptibility in humans appears to be independent of inflammatory cytokines and/or activated T cells. Altogether, these results suggest MPA-induced hypo-estrogenism may alter key metabolic components that are necessary for vaginal colonization by certain bacterial species including lactobacilli, and allow for greater bacterial diversity in the vaginal microbiota.
2019-10-17 | GSE138971 | GEO
Project description:Agilent 4x44k Whole Mouse Genome v1 Microarrays were used to analyze aortic transcriptome of mice substituted with medroxyprogesterone acetate, norethisterone acetate or placebo after having been ovariectomized. The aim of this experiment was to detect genes regulated in the gestagen-treated groups as compared to placebo that might be involved in thrombotic events
2014-06-30 | GSE57972 | GEO
Project description:Cells were cotreated with dihydrotestosterone, progesterone or medroxyprogesterone acetate and estrdiol to assess the combinatorial effects of hormone exposure in breast cancer cells
2015-10-18 | GSE61368 | GEO