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Related Experiment Video

Updated: Feb 3, 2026

Murine Orchiectomy and Ovariectomy to Reduce Sex Hormone Production

Murine Orchiectomy and Ovariectomy to Reduce Sex Hormone Production

Published on: November 17, 2023

Sex Hormones Regulate SHANK Expression.

Simone Berkel¹, Ahmed Eltokhi^1,2, Henning Fröhlich¹

¹Department of Human Molecular Genetics, Institute of Human Genetics, Ruprecht-Karls-University, Heidelberg, Germany.

Frontiers in Molecular Neuroscience

|October 16, 2018

Summary

This summary is machine-generated.

Sex hormones significantly impact SHANK gene expression, a key factor in autism spectrum disorder (ASD). This study reveals sex-differential SHANK protein levels in the brain, offering new insights into ASD's male predominance.

Keywords:

17β-estradiol SH-SY5Y cells SHANK androgen receptor knock-out mouse autism spectrum disorders (ASD)dihydrotestosterone sex differences

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Published on: July 28, 2023

Area of Science:

Neuroscience
Genetics
Endocrinology

Background:

Autism spectrum disorder (ASD) exhibits a higher prevalence in males (4:1 ratio).
SHANK genes (SHANK1, SHANK2, SHANK3) encode postsynaptic scaffolding proteins strongly linked to ASD.
Early brain development is significantly influenced by sex hormones.

Purpose of the Study:

To investigate the effects of dihydrotestosterone (DHT) and 17β-estradiol on SHANK gene expression.
To explore the role of sex hormones in the sex-differential expression of SHANK genes.
To provide insights into the neurobiological basis of ASD sex bias.

Main Methods:

Utilized a human neuroblastoma cell model to study SHANK gene expression under hormonal influence.
Employed androgen and estrogen receptor antagonists to block hormonal effects.
Examined SHANK gene expression in neuron-specific androgen receptor knock-out mice (ArNesCre).
Analyzed sex-differential SHANK protein expression in wild-type (WT) mouse cortex at embryonic and postnatal stages.

Main Results:

Both DHT and 17β-estradiol significantly impacted the expression of all three SHANK genes.
Hormonal effects on SHANK expression were blocked by specific receptor antagonists.
A nominal reduction in SHANK genes was observed in neuron-specific androgen receptor knock-out mice.
Significantly higher SHANK protein levels were found in male compared to female mice in the developing cortex.

Conclusions:

SHANK gene expression is demonstrably influenced by sex hormones.
Sex hormones contribute to sex-differential SHANK expression, potentially explaining ASD sex bias.
Findings offer novel insights into the genetic and hormonal underpinnings of sex differences in ASD.