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Molecular androgen memory in sex development.

Paul-Martin Holterhus¹

¹Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, Christian-Albrechts-University of Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. holterhus@pediatrics.uni-kiel.de

Pediatric Endocrinology Reviews : PER

|March 20, 2012

Summary

Androgens, acting through the androgen receptor, drive sex-specific development from embryogenesis through puberty. Evidence suggests a molecular "androgen memory" exists at the gene expression and epigenome levels, influencing long-term anatomical and functional changes.

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Area of Science:

Developmental Biology
Endocrinology
Genetics

Background:

Human sex-specific development involves irreversible changes in genitalia, secondary sex characteristics, and extragenital tissues, including the brain.
Androgens, mediated by the androgen receptor, are critical regulators of these developmental processes.
While androgens induce reversible gene transcription changes, their long-term impact on development is often irreversible.

Purpose of the Study:

To explore the role of androgens and the androgen receptor in sex-specific human development.
To investigate the molecular mechanisms underlying both short-term and long-term effects of androgens.
To examine evidence for a molecular memory of androgen action at the transcriptome and epigenome levels.

Main Methods:

Review of existing literature on sex-specific development and androgen action.
Analysis of recent genome-wide gene expression studies.
Discussion of emerging experimental data at the epigenome level.

Main Results:

Androgens play a pivotal role in sexual differentiation and maturation throughout human development.
Single-cell studies show androgens induce reversible changes in gene transcription via androgen receptor activation.
Developmental effects of androgens can lead to irreversible anatomical and functional changes.

Conclusions:

There is compelling evidence for a molecular "androgen memory" that persists at both the transcriptome and epigenome levels.
This molecular memory contributes to the establishment of irreversible sex-specific traits.
Understanding androgen memory is crucial for comprehending human development and potential endocrine disruptions.