| My thesis work was to examine the hypothesis that during early development sexually dimorphic expression of the genes associated with RNA processing in the mouse cortex and hippocampus is regulated by perinatal testosterone to activate estrogen receptors (ERs) after its conversion to estradiol via aromatase within the brain, which might create differences in mRNA variants of their targets between the sexes, and then lead to sexual dimorphism in structure and function of these brain regions. To test this, I first used reverse transcriptase with quantitative PCR to measure relative mRNA levels of 14 selected candidate genes, encoding RNA binding proteins, in the cortex/hippocampus of male and female mice collected on the day of birth (PN0), and 7 (PN7), 14 (PN14), and 21 (PN21) days after birth. A significant sex difference in mRNA levels of Khdrbs2, Nanos2, Rbm48, and Tdrd3 was observed, and females expressed more Rbm48 and Tdrd3 mRNA on PN0 and PN7 than males. Of these genes, the female-biased expression of Rbm48 in neonates was abolished by prenatal exposure to testosterone propionate via down-regulation of Rbm48 mRNA levels in females, but postnatal exposure to testosterone propionate during PN21-23 increased Rbm48 expression in both sexes. Surprisingly, neonatal exposure to estradiol benzoate abolished the sex difference in Rbm48 expression by up-regulating Rbm48 mRNA levels in males. These results suggest that hormonally regulated expression of Rbm48 presents a novel molecular mechanism underlying the development of sexual dimorphism in cortical and hippocampal structure and function. |
