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The effects of testosterone on gene expression of cell‐adhesion molecules and scaffolding proteins: The role of sex in early development

Sex‐specific differences in brain plasticity appear to be organised by testosterone, which is particularly important during the early stages of development. The main purpose of the present study was to examine the sex differences in mRNA and protein levels of selected cell‐adhesion molecules and scaffolding proteins on postnatal days 5 (P5) and 9 (P9) in the rat hippocampus, as well as evaluate the effects of testosterone treatment (100 nM, 48 hr) on synaptic proteins in SH‐SY5Y (neuron‐like) and U‐87MG (astrocyte‐like) cells. The gene expression levels of Neuroligin 3 and ‘SH3 and multiple ankyrin repeat domains protein’ 1 and 3 (SHANK1 and SHANK3) were significantly lower in males compared to females at P5. At P9, a similar significant trend towards a decrease in mRNA expression and protein levels of SHANK3 was found in males. Testosterone treatment induced a significant decrease of Neuroligin 1‐3 mRNA expression in both SH‐SY5Y and U‐87MG cells. SHANK1 and SHANK3 mRNA levels significantly decreased in U‐87MG cells response to testosterone presence. The presented results demonstrate that the association of selected postsynaptic cell‐adhesion molecules and scaffolding proteins is sex‐related. Testosterone appears to be particularly involved in the developmental mechanisms related to neuroplasticity.