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Dihydrotestosterone induces minor transcriptional alterations in genital skin fibroblasts of normal prepubertal boys

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE121712 | GEO | 2019/03/01

REPOSITORIES: GEO

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