Effects of androgen treatment on genital fibroblasts
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE3871 | GEO | 2005/12/21
SECONDARY ACCESSION(S): PRJNA104855
REPOSITORIES: GEO
Similar Datasets
Project description:Endogenous and exogenous androgens induce masculinization of external genitalia through binding to the androgen receptor (AR). Although several efforts were made to determine the androgen target genes in external genitalia by analyzing transcript profiles in cultured genital skin fibroblasts, no genes except for APOD were shown to be significantly regulated by androgens. In the present study, we performed microarray analysis for genital skin fibroblasts obtained from four boys with buried penis (the control individuals) and a patient with androgen insensitivity syndrome (AIS) due to a hypomorphic mutation in AR (the AIS patient). We identified 26 transcripts which were upregulated or downregulated by dihydrotestosterone (DHT) in all samples of control individuals and, to a lesser extent, in the sample of the AIS patient. None of the transcripts showed statistically significant differences between DHT-treated and -untreated samples. The 26 transcripts included CYP1B1, a gene possibly involved in the development of genital tubercle in mice, and APOD, as well as several genes that have been reported as androgen targets in prostate or other tissues. Realtime PCR analyses detected a significant difference in the effects of DHT on APOD expression between the AIS patient and the control individuals, while the difference in the fold changes of CYP1B1 expression were negligible. The results of this study indicate that DHT mediates masculinization of external genitalia through minor transcriptional changes of several genes, rather than massive changes in specific genes. In addition, our data confirm the clinical importance of APOD as a biomarker for AR function.
2019-03-01 | GSE121712 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE3871: Effects of androgen treatment on genital fibroblasts GSE3872: Baseline gene transcription in genital fibroblasts Abstract: BACKGROUND: Androgen insensitivity syndrome (AIS) comprises a range of phenotypes from male infertility to complete feminization. Most individuals with AIS carry germline mutations of the androgen receptor (AR) that interfere with or ablate its function. As genital fibroblasts retain expression of the AR in vitro, we used genital skin fibroblasts from normal males and 46,XY females with complete AIS due to known AR mutations to gain insights into the role of the AR in human genital differentiation. RESULTS: Using DNA microarrays representing 32,968 different genes, we identified 404 transcripts with significant differences in transcription levels between genital skin fibroblasts cultured from normal and AIS-affected individuals. Gene-cluster analyses uncovered coordinated expression of genes involved in key processes of morphogenesis. On the basis of animal studies and human genetic syndromes, several of these genes are known to have specific roles in genital differentiation. Remarkably, genital fibroblasts from both normal and AIS-affected individuals showed no transcriptional response to dihydrotestosterone treatment despite expression of the AR. CONCLUSIONS: The results suggest that in addition to differences in the anatomic origin of the cells, androgen signaling during prenatal development contributes to setting long-lasting, androgen-independent transcriptional programs in genital fibroblasts. Our findings have broad implications in understanding the establishment and the stability of sexual dimorphism in human genital development. Refer to individual Series
2006-03-06 | E-GEOD-4353 | biostudies-arrayexpress
Project description:Abstract: BACKGROUND: Androgen insensitivity syndrome (AIS) comprises a range of phenotypes from male infertility to complete feminization. Most individuals with AIS carry germline mutations of the androgen receptor (AR) that interfere with or ablate its function. As genital fibroblasts retain expression of the AR in vitro, we used genital skin fibroblasts from normal males and 46,XY females with complete AIS due to known AR mutations to gain insights into the role of the AR in human genital differentiation. RESULTS: Using DNA microarrays representing 32,968 different genes, we identified 404 transcripts with significant differences in transcription levels between genital skin fibroblasts cultured from normal and AIS-affected individuals. Gene-cluster analyses uncovered coordinated expression of genes involved in key processes of morphogenesis. On the basis of animal studies and human genetic syndromes, several of these genes are known to have specific roles in genital differentiation. Remarkably, genital fibroblasts from both normal and AIS-affected individuals showed no transcriptional response to dihydrotestosterone treatment despite expression of the AR. CONCLUSIONS: The results suggest that in addition to differences in the anatomic origin of the cells, androgen signaling during prenatal development contributes to setting long-lasting, androgen-independent transcriptional programs in genital fibroblasts. Our findings have broad implications in understanding the establishment and the stability of sexual dimorphism in human genital development. This SuperSeries is composed of the SubSeries listed below.
2006-03-07 | GSE4353 | GEO
Project description:LNCaP cells are an established androgen receptor expressing prostate carcinoma cell line. Human foreskin fibroblasts also expressing the androgen receptor were obtained from phenotypic normal male individuals. Cells were cultured either at confluency leading to G0 cell cycle state or while they were proliferating. Cells were either untreated, or treated with dihydrotestosterone (DHT) or ethanol (ETOH) which also served as the solvent for the DHT. All experimental RNA samples derived from the untreated or treated cell lines were hybridized on cDNA arrays against a common reference. This reference was composed out of common reference CRG (50%) and out of fibroblast RNA (50%). This reference is also called "mixed reference" in the description of the 26 individual experiments. A strain or line experiment design type assays differences between multiple strains, cultivars, serovars, isolates, lines from organisms of a single species. Compound Based Treatment: dihydrotestosterone (DHT) or ethanol (ETOH = solvent) Cell Line: genital fibroblast cell line or prostate carcinoma cell line (LNCaP) Culture Synchrony: Go or proliferation Keywords: strain_or_line_design
2006-10-12 | GSE4453 | GEO
Project description:LNCaP cells are an established androgen receptor expressing prostate carcinoma cell line. Human foreskin fibroblasts also expressing the androgen receptor were obtained from phenotypic normal male individuals. Cells were cultured either at confluency leading to G0 cell cycle state or while they were proliferating. Cells were either untreated, or treated with dihydrotestosterone (DHT) or ethanol (ETOH) which also served as the solvent for the DHT. All experimental RNA samples derived from the untreated or treated cell lines were hybridized on cDNA arrays against a common reference. This reference was composed out of common reference CRG (50%) and out of fibroblast RNA (50%). This reference is also called "mixed reference" in the description of the 26 individual experiments. A strain or line experiment design type assays differences between multiple strains, cultivars, serovars, isolates, lines from organisms of a single species. Compound Based Treatment: dihydrotestosterone (DHT) or ethanol (ETOH = solvent) Cell Line: genital fibroblast cell line or prostate carcinoma cell line (LNCaP) Culture Synchrony: Go or proliferation Computed
2006-10-12 | E-GEOD-4453 | biostudies-arrayexpress
Project description:The text description is: LNCaP are androgen receptor expressing prostate carcinoma cells. Genital skin fibroblasts also express the androgen receptor. Cells were either proliferating or they were G0-arrested. Treatment of cells was performed with either the androgen DHT (dihydrotestosterone), the androgen analogue R1881 (methyltrienolone), or the solvent ethanol. Some hybridizations were performed in the type 1 design. In these cases, the hormone treated sample was hybridized against the ethanol treated sample on the same microarray. Hormone mediated induction or repression of gene transcription can directly be deduced from R/G normalized ratios on arrays. For other experiments, the ethanol treated control and the hormone treated experiment were hybridized on separate microarrays against a common reference of RNA. This reference was composed out of common reference batch CRG (50%) and a fibroblast RNA (50%). This reference was called mixed reference. For all experiments, the same batch of mixed reference was used. A compound treatment design type is where the response to administration of a compound or chemical (including biological compounds such as hormones) is assayed. Compound Based Treatment: Ethanol, R1881 (methyltrienolone), or DHT (dihydrotestosterone) Cell Line: LNCaP (prostate cancer) or foreskin fibroblasts Culture Synchrony: proliferation / Go-arrest Keywords: compound_treatment_design
2006-10-12 | GSE4454 | GEO
Project description:The text description is: LNCaP are androgen receptor expressing prostate carcinoma cells. Genital skin fibroblasts also express the androgen receptor. Cells were either proliferating or they were G0-arrested. Treatment of cells was performed with either the androgen DHT (dihydrotestosterone), the androgen analogue R1881 (methyltrienolone), or the solvent ethanol. Some hybridizations were performed in the type 1 design. In these cases, the hormone treated sample was hybridized against the ethanol treated sample on the same microarray. Hormone mediated induction or repression of gene transcription can directly be deduced from R/G normalized ratios on arrays. For other experiments, the ethanol treated control and the hormone treated experiment were hybridized on separate microarrays against a common reference of RNA. This reference was composed out of common reference batch CRG (50%) and a fibroblast RNA (50%). This reference was called mixed reference. For all experiments, the same batch of mixed reference was used. A compound treatment design type is where the response to administration of a compound or chemical (including biological compounds such as hormones) is assayed. Compound Based Treatment: Ethanol, R1881 (methyltrienolone), or DHT (dihydrotestosterone) Cell Line: LNCaP (prostate cancer) or foreskin fibroblasts Culture Synchrony: proliferation / Go-arrest Computed
2010-07-01 | E-GEOD-4454 | biostudies-arrayexpress
Project description:To identify the genes which have relation to aromatase-inhibitor-resistance, we compared the gene expression of aromatase-inhibitor-resistant cell, A3, with that of parent cell line, T-47D. Because A3 showed remarkable cell proliferation by 1nM Dihydrotestosterone(DHT), cells were cultured with DHTand bicalutamide for 24h, and total RNA was extracted.
2014-04-01 | E-GEOD-51390 | biostudies-arrayexpress
Project description:This dataset contains fibroblasts from different genital and extragenital regions, mostly from 46,XY individuals. Due to proven androgen receptor gene mutations, several individuals have varying degrees of undervirilization of the external genitalia ranging from complete androgen insensitivity syndrome (CAIS) to partial androgen insensitivity syndrome (PAIS). CAIS is a completely female person despite a 46,XY karyotype. AIS-3 individuals have ambigous external genitalia. AIS-4 means predominantly female (clitoral enlargement), AIS-2 means predominantly male (hypospadias). It is important for this experiment set, that it contains data from 3 differet independent datasets that are not directly cmparable with each other. This is because of different reference RNAs and different glass slides. The particular normalization procedure is described in the paper accompanying this dataset. Only then, all arrays are allowed to be clustered together. Dataset 2 and 3 have "DS-2" and "DS-3" in their experiment names. All other experiments belong to dataset 1. A cell type comparison design experiment design type compares cells of different type for example different cell lines. Disease State: normal male, normal female or ambiguous external genitalia according to grading scheme by Sinnecker et al. Cell Line: fibroblast cell lines from different regions of the genital skin, some from extragenital skin Sex/Mating type: 46,XY or 46,XX karyotype Computed
2010-06-25 | E-GEOD-6796 | biostudies-arrayexpress
Project description:Human scrotum and labia majora samples treated with DHT and/or AZA A compound treatment design type is where the response to administration of a compound or chemical (including biological compounds such as hormones) is assayed. Compound Based Treatment: dihydrotestosterone (DHT), 5-aza-deoxy-cytidine (AZA), none or both Cell Line: normal scrotum or labia majora derived from complete androgen insensitivity syndrome due to inactivating mutation of the androgen receptor gene
2009-05-20 | GSE11847 | GEO