The differential role of androgens in early human sex development
Open accessAbstract
Sexual development in humans is only partly understood at the molecular level. It is dependent on genetic control primarily induced by the sex chromosomal differences between males and females. This leads to the development of the gonads, whereby afterwards the differentiation of the apparent phenotype is controlled by hormone action. Sex steroids may exert permanent and temporary effects. Their organizational features of inducing permanent changes in phenotype occur through genetic control of downstream genes. In this, androgens are the key elements for the differentiation of male internal and external genitalia as well as other sexual organs and general body composition, acting through a single androgen receptor. The androgen receptor is a nuclear transcription factor modulating DNA transcription of respective target genes and thereby driving development and growth in a stringent manner. The specificity of androgen action seems to be a strictly time-controlled process with the androgen receptor acting in concert with different metabolites and an array of cofactors modulating the cellular response and thereby permanently altering the phenotype of any given individual. For every cell programmed by androgens, a specific 'androgen response index' must be proposed.
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Sex determination is led by genes on sex chromosomes and release of sex hormones, especially androgens and estrogens, primarily from gonads, exerting effects on body, brain, and behavior.
“This process is led by genes located on the sex chromosomes and the release of sex hormones, especially androgens and estrogens, coming primarily from the gonads and exerting effects on the body, brain, and behavior [10–13].”
From Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus (2025) · cites this paper as [12]
The Introduction’s developmental-aspects section links X- and Y-chromosome genes to sexual development, describes hormones secreted mainly by the testes, and reports sex-steroid effects on the body, brain, and behavior. The paper specifically discusses androgens, but the cited passages do not substantiate the claim’s added emphasis on estrogens. (LLM, conf=0.84)
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- Authors
- Hiort, O.
- Affiliations
- University of Lübeck (DE)
- Corresponding author
- Hiort, Olaf
- ORCID
- Hiort, Olaf
- Venue
- BMC Medicine
- Published
- 2013-06-24
- Volume
- 11
- Issue
- 1
- Pages
- 152-152
- ISSN
- 1741-7015 (ISSN-L)
- PMC
- PMC3706224
- OpenAlex
- W1973733021
- Cited by
- 87
- References
- 42
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 10 · 2023: 3 · 2022: 13 · 2021: 7 · 2020: 7 · 2019: 6 · 2018: 10 · 2017: 7 · 2016: 4 · 2015: 3 · 2014: 5 · 2013: 1
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- European Commission (201444)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- androgens, androgen receptor, gonadal differentiation, sex determination, transcriptional regulation, cofactors, body composition
- MeSH terms
- Androgens, Animals, Cell Differentiation, Female, Humans, Male, Sex Differentiation, Disorders of Sex Development, Sexual Development
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