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Cited by 118Urological Disorders and TreatmentsSexual Differentiation and DisordersGenital Health and Disease

Expression of the androgen receptor and 5α-reductase type 2 in the developing human fetal penis and urethra

Kim, Kun, Liu, Wenhui, Cunha, Gerald R., Russell, David W., Huang, Hongying, Shapiro, Ellen, Baskin, Laurence S.·2002·Cell and Tissue Research
DOI 10.1007/s004410100464
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Abstract

Normal penile development is dependent on testosterone, its conversion via steroid 5 alpha-reductase type 2 to dihydrotestosterone, and a functional androgen receptor (AR). The goal of this study was to investigate the distribution of AR and 5 alpha-reductase type 2 in the developing human fetal external genitalia with special emphasis on urethra formation. Twenty fetal genital specimens from normal human males (12-20 weeks gestation) were sectioned serially and stained by avidin-biotinylated peroxidase complex method with antigen retrieval. Stained sections throughout male genital development documented the expression of AR and 5 alpha-reductase type 2 in the phallus. Between 12 and 14 weeks of gestation, AR was localized to epithelial cells of the urethral plate in the glans, the tubular urethra of the penile shaft, and stromal tissue surrounding the urethral epithelium. In the fetal penis between 16 and 20 weeks gestation, the density of AR expression was greatest in urethral epithelial cells versus the surrounding stromal tissues. There was a characteristic pattern of AR expression in the glandular urethral epithelium between 16 and 20 weeks gestation. AR expression was greater along the ventral aspect of the glandular urethra than along the dorsal aspect of the urethral epithelium. The expression of 5 alpha-reductase type 2 was localized to the stroma surrounding the urethra, especially along the urethral seam area in the ventral portion of the remodeling urethra. These anatomical studies support the hypothesis that androgens are essential for the formation of the ventral portion of the urethra and that abnormalities in either the AR or 5 alpha-reductase type 2 can explain the occurrence of hypospadias.

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  • Estradiol, dihydrotestosterone, and 3-alpha androstanediol have established roles in reproductive, bone, hepatic, renal, cardiovascular, dermatologic, prostatic, penile, and central nervous system functions.

    “Estradiol, DHT, and the DHT product, 3-alpha androstanediol have established roles in reproductive, bone, hepatic, renal, cardiovascular, dermatologic, prostatic, penile, and central nervous system functions, among others.”

    From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [17]

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Authors
Kim, K., Liu, W., Cunha, G. R., Russell, D. W., Huang, H., Shapiro, E., & Baskin, L. S.
Affiliations
  • University of California, San Francisco (US)
  • The University of Texas Southwestern Medical Center (US)
  • New York University (US)
ORCID
Venue
Cell and Tissue Research
Publisher
Springer Science and Business Media LLC
Published
2001-11-27
Volume
307
Issue
2
Pages
145-153
ISSN
  • 0302-766X (ISSN-L)
  • 1432-0878
DOI
10.1007/s004410100464
OpenAlex
W2135747955
Cited by
118
References
21
Citations by year
2025: 2 · 2024: 6 · 2023: 8 · 2022: 6 · 2021: 4 · 2020: 5 · 2019: 4 · 2018: 7 · 2017: 4 · 2016: 8 · 2015: 6 · 2014: 7 · 2013: 6 · 2012: 6
FWCI
3.60
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Cell and Tissue Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Urology › Urological Disorders and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Health Sciences › Medicine › Surgery › Genital Health and Disease
Keywords
androgen receptor, 5α-reductase type 2, penile development, dihydrotestosterone, urethral epithelium, hypospadias, androgen signaling, male genital development
MeSH terms
Embryonic and Fetal Development, Humans, Male, Penis, Receptors, Androgen, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase, Tissue Distribution, Urethra

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