Dihydrotestosterone induces minor transcriptional alterations in genital skin fibroblasts of children with and without androgen insensitivity
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- Tanase-Nakao Kanako
- Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan Department of Advanced Pediatric Medicine, Tohoku University School of Medicine, Tokyo 157-8535, Japan
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- Mizuno Kentaro
- Department of Pediatric Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
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- Hayashi Yutaro
- Department of Pediatric Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
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- Kojima Yoshiyuki
- Department of Urology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan
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- Hara Mariko
- Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan
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- Matsumoto Kenji
- Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan
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- Matsubara Yoichi
- Department of Advanced Pediatric Medicine, Tohoku University School of Medicine, Tokyo 157-8535, Japan Institute director, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan
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- Igarashi Maki
- Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan
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- Miyado Mami
- Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan
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- Fukami Maki
- Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan
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Abstract
<p>Endogenous and exogenous androgens induce masculinization of external genitalia through binding to the androgen receptor (AR). The target genes of androgens in external genitalia remain to be determined, although previous studies have shown that the apolipoprotein D gene (APOD) was significantly upregulated by dihydrotestosterone (DHT), the most potent androgen in humans. 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 partial androgen insensitivity syndrome (PAIS) due to a hypomorphic mutation in AR (the PAIS patient). We identified 24 transcripts that were upregulated or downregulated by DHT in all samples of control individuals and, to a lesser extent, in the sample of the PAIS patient. Differences between DHT-treated and -untreated samples were small; the results of 24 transcripts did not reach statistical significance. The 24 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. The results of this study indicate that androgen-mediated masculinization of external genitalia is unlikely to depend on massive transcriptional changes in specific AR target genes. Rather, minor transcriptional changes of several genes, and/or a complex molecular network may play a major role in penile development. Importantly, our data suggest the possible involvement of CYP1B1 in human genital development and confirm the clinical importance of APOD as a biomarker for AR function.</p>
Journal
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- Endocrine Journal
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Endocrine Journal 66 (4), 387-393, 2019
The Japan Endocrine Society