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The Phytoestrogen Genistein Is a Tissue-Specific Androgen Receptor Modulator

ABSTRACT: We report that the phytoestrogen genistein acts as a tissue-specific androgen receptor modulator in mouse using a novel androgen reporter mouse line and gene expression profiling. Genistein is a partial androgen agonist/antagonist in prostate, brain, and testis but not in skeletal muscle or lung. Gene expression profiling has been done from prostates of intact and castrated male mice treated with genistein or vehicle. Gene expression profiling was also done from prostates of estradiol-treated intact male mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE31341 | GEO | 2011/08/19

SECONDARY ACCESSION(S): PRJNA145925

REPOSITORIES: GEO

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The Phytoestrogen Genistein Is a Tissue-Specific Androgen Receptor Modulator

Project description:We report that the phytoestrogen genistein acts as a tissue-specific androgen receptor modulator in mouse using a novel androgen reporter mouse line and gene expression profiling. Genistein is a partial androgen agonist/antagonist in prostate, brain, and testis but not in skeletal muscle or lung. Gene expression profiling has been done from prostates of intact and castrated male mice treated with genistein or vehicle. Gene expression profiling was also done from prostates of estradiol-treated intact male mice. Gene expression profiling from prostates of castrated and intact male mice after 5-day genistein- or vehicle-treatment or after 4-day estradiol- or vehicle-treatment.

2011-08-18 | E-GEOD-31341 | biostudies-arrayexpress

Comparison of prostate epithelial cells from intact and castrated mice

Project description:Androgen is critical for the growth of the murine prostate. Castration removes the predominant source of androgen in the mouse, leading to prostatic atrophy and death of epithelial cells. However, studies show that epithelial cells which remain in the castrated prostate are enriched for progenitor activity compared to the intact prostate. We performed gene expression profiling of basal and luminal epithelial cells isolated from paired intact and castrated adult male C57BL/6 mouse prostates to gain insights into the mechanisms promoting survival in castration-resistant epithelial cells.

2015-12-03 | GSE75628 | GEO

Transcription profiling of mouse uterine response to estrogen 17-beta-estradiol, the phytoestrogen genistein, and the synthetic estrogen diethylstilbestrol

Project description:We used gene expression profiling to investigate whether the molecular effects induced by estrogens of different provenance are intrinsically similar. In this article we show that the physiologic estrogen 17-beta-estradiol, the phytoestrogen genistein, and the synthetic estrogen diethylstilbestrol alter the expression of the same 179 genes in the intact immature mouse uterus under conditions where each chemical has produced an equivalent gravimetric and histologic uterotrophic effect, using the standard 3-day assay protocol. Data are also presented indicating the limitations associated with comparison of gene expression profiles for different chemicals at times before the uterotrophic effects are fully realized. We conclude that the case has yet to be made for regarding synthetic estrogens as presenting a unique human hazard compared with phytoestrogens and physiologic estrogens. Key words: diethylstilbestrol, estrogen, gene expression, genistein, microarray, phytoestrogen, toxicogenomics, uterus.

2022-11-20 | E-AFMX-13 | biostudies-arrayexpress

Single Cell Analysis Reveals The Essential Role of TGFbeta Pathway in Shaping Immune-suppressive Microenvironment and Promoting nmCRPC Development (bulk RNA-Seq)

Project description:To understand the dynamic changes of different cell populations within the Pten-null prostate cancer model in response to ADT, we carried out scRNA-seq transcriptome analysis on CD45- and CD45+ FACS-sorted cells from Pten-null intact (CP), early-(nmCRPC-4wks) and late-(nmCRPC-12wks) stage castrated prostates, respectively. To systematically investigate the effects of androgen deprivation therapy (ADT) on the cellular landscapes of primary and nmCRPC as well as intra- and extra-tumoral immune cells and their functional status at single cell level, we conducted scRNA-seq on CD45+ cells from bone marrow, blood, spleen and thymus of intact, early- and late-stage castrated Pten-null mice.

2024-11-29 | GSE270743 | GEO

A quantitative proteomic based approach to study the genistein induced epigenetic reprogramming in MDA-MB231 cells

Project description:Epidemiological data indicate that consumption of soy-based food significantly reduces the cancer risk in human through interaction with estrogen receptors and the ‘phytoestrogen’ genistein present in the soy is responsible for this chemopreventive activity. The epigenome regulatory effect of genistein also reported but the key mechanism behind this effect remain elusive. In this current project, we reported the epigenome modulation effect of genistein using MDA-MB231 cells. Cells were treated with low-dose genistein for >1 month and the stable epigenetic alterations were analyzed by partial MNase digestion and TMT-based quantitative proteomics based chromatome mapping approach. We identified a total of 3177 chromatin-bound proteins with high confidence, including 882 proteins that displayed altered binding topology after cell conditioning with genistein. Prolonged phytochemical exposure permanently modified the binding topology of the key epigenetic regulators and preserved their binding topology in untreated progeny. Genistein induced altered epigenome modulation negatively regulates the expression of cell proliferation genes and suppress cell growth. In contrast, previously exposed cells displayed reduced expression of DNA repair genes and enhanced genotoxic stress upon genistein withdrawal.

2018-07-05 | PXD006178 | Pride

The effect of GPR30 agonist G-1 on androgen-sensitive and castration-resistant LNCaP xenografts

Project description:G-1 is an agonist to GPR30. Activation of GPR30 by G-1 inhibited prostate cancer cell growth in LNCaP xenografts regrown after catration of the host (nude mice), but not in the androgen-sensitive LNCaP xenograft grown in an intact host. Results provide insights into the molecular basis of G-1 action in castration-resistant prostate cancer. Male nude mice were injected with LNCaP cells. When the LNCaP tumors reached 150–300 mm3, mice were divided into two groups: intact (androgen-sensitive tumor) and castrated. For the intact group, mice were subcutaneously injected with vehicle alone (95% PBS, 2.5% DMSO, 2.5% ethanol) or G-1 (4 mg/kg/day in vehicle) daily for 16 days. For the castrated group, tumors regressed and then regrew to ~300-400mm3. Mice were treated daily with vehicle or G-1 as described for 16 days. Tumors were harvested for RNA extraction and microarray experiments.

2014-02-14 | E-GEOD-54974 | biostudies-arrayexpress

Mus musculus

Project description:The Phytoestrogen Genistein Is a Tissue-Specific Androgen Receptor Modulator

| PRJNA145925 | ENA

The impact of a phytoestrogen-rich diet on cardiac gene expression in the context of HCM

Project description:A soy diet worsens the progression of an inherited form of hypertrophic cardiomyopathy (HCM) in male mice when compared to casein-fed mice. Females are largely resistant to this diet effect and better preserve cardiac function. We hypothesized that the abundant phytoestrogens found in soy are mainly responsible for this diet-dependent phenotype. Indeed, feeding male mice a phytoestrogen-supplemented casein-based diet can recapitulate the negative outcome seen when male mice are fed a standard soy-based diet. To gain mechanistic insights into disease pathogenesis, we used Affymetrix microarrays to profile gene expression in left ventricular tissue from 2 month old HCM male and female mice as well as wild-type littermate controls. These mice were fed a phytoestrogen (genistein + daidzein)-supplemented casein-based diet. We identified a number of molecular pathways that could explain both the male and female phenotypes. Hearts from male and female wild-type or HCM C57BL/6 mice fed a phytoestrogen-supplemented (genistein and daidzein mix) casein-based diet were excised at 2 months of age. Total RNA was extracted from left ventricles. Biotin-labeled amplified RNA was hybridized to Affymetrix Mouse Genome 430 2.0 microarrays.

2011-06-02 | E-GEOD-29648 | biostudies-arrayexpress

A folic acid-enriched diet attenuates prostate involution in response to androgen deprivation

Project description:Folic acid is present in pre-natal vitamins, fortified cereal grains and multi-vitamin supplements. High intake of folic acid through these sources has resulted in populations with increased levels of serum folate and unmetabolized folic acid. Although the benefits of folic acid in the prevention of neural tube defects are undeniable, the impact of long-term consumption of folic acid on the prostate is not fully understood. In this study, we used a rodent model to test whether dietary folic acid (FA) supplementation changes prostate homeostasis and response to androgen deprivation. Although intact prostate weights do not differ between diet groups, we made the surprising observation that dietary folic acid supplementation confers partial resistance to castration-mediated prostate involution. More specifically, male mice that were fed a folic acid supplemented diet and then castrated had greater prostate wet weights, greater prostatic luminal epithelial cell heights, and more abundant RNAs encoding prostate secretory proteins compared to mice that were fed a control diet and castrated. We used RNA-seq to identify signaling pathways enriched in the castrated prostates from folic acid supplemented diet fed mice compared to control mice. We observed differential expression of genes involved in several metabolic pathways in the FA supplemented mice. Together, our results show that dietary FA supplementation can impact metabolism in the prostate and attenuate the prostate’s response to androgen deprivation. This has important implications for androgen deprivation therapies used in the treatment of prostate disease, as consumption of high levels of folic acid could reduce the efficacy of these treatments.

2018-08-22 | GSE116299 | GEO

Hepatic transcriptome changes in testosterone-deficient pigs fed a high-fat diet

Project description:To gain insight into the role of testosterone in modulating hepatic fat accumulation, we collected liver tissues from high fat diet-fed intact male pigs, castrated male pigs, and castrated male pigs with testosterone replacement. RNA-Seq was employed to profile hepatic gene expression in pigs with different testosterone levels. Liver mRNA profiles of intact male pigs fed a HFC diet, castrated male pigs fed a HFC diet, and castrated male pigs treated with testosterone fed a HFC diet were generated by deep sequencing, using Illumina HiSeq 2000.

2015-01-08 | E-GEOD-62696 | biostudies-arrayexpress

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