Age- and Sex-Dependent Changes in Androgen Receptor Expression in the Developing Mouse Cortex and Hippocampus

Area of Science:

• Neuroscience
• Developmental Biology
• Endocrinology

Background:

• Testosterone (T) exposure during the perinatal period drives sexual dimorphism in brain structures and behaviors.
• Testosterone acts directly via androgen receptors (AR) and indirectly through estrogen receptors after aromatization in the brain.

Purpose of the Study:

• To investigate whether androgen receptor (AR) expression in the developing mouse cortex and hippocampus exhibits sexual dimorphism.
• To correlate AR expression patterns with known sex differences in circulating testosterone levels.

Main Methods:

• Quantification of AR mRNA and protein levels in mouse cortex and hippocampus at postnatal days 0, 7, 14, and 21.
• Detection of full-length (110 kDa) and smaller (70 kDa) AR protein isoforms using Western blotting or similar techniques.

Main Results:

• AR mRNA levels increased with age in both sexes, with no significant sex difference observed.
• Both AR protein isoforms showed age-dependent increases, peaking at postnatal day 21.
• A transient, masculine-specific increase in full-length AR protein expression was detected on postnatal day 7.

Conclusions:

• Postnatal age and sex-specific differences in AR protein expression, alongside sex differences in circulating testosterone, likely contribute to the sexual differentiation of the mouse cortex and hippocampus.
• The findings highlight the complex interplay between hormones and gene expression in shaping sex differences in the developing brain.