Androgenic regulation of sexually dimorphic expression of RNA binding motif protein 48 in the developing mouse cortex and hippocampus

Abstract

To further reveal the molecular mechanism underlying sexual differentiation of the mouse cerebral cortex and hippocampus, we reanalyzed our previous microarray study with Gene Ontology (GO) term enrichment and found that the GO term “RNA binding” was over‐represented among the 89 sexually dimorphic candidate genes. Thus, we selected 16 autosomal genes annotated to the term RNA binding and profiled their mRNA expression in the developing male and female mouse cortex/hippocampus. During the first three weeks after birth, sex differences in mRNA levels of Khdrbs2, Nanos2, Rbm48, and Tdrd3 were observed in the mouse cortex/hippocampus. Of these genes, only the female‐biased expression of Rbm48 in neonates was abolished by prenatal exposure to testosterone propionate (TP), while postnatal treatment of TP three weeks after birth increased Rbm48 and Tdrd3 mRNA levels in both sexes. Regardless of sex, the postnatal cortex/hippocampus also showed a marked increase in the content of androgen receptor (Ar) and estrogen receptor β (Esr2), but a decrease in estrogen receptor α (Esr1) and aromatase (Cyp19a1), which might confer the different responses of Rbm48 to prenatal and postnatal TP. Our results suggest that androgen‐regulated, sexually dimorphic Rbm48 expression might present a novel molecular mechanism by which perinatal androgens control development of sexual dimorphism in cortical and hippocampal structure and function.

Estrogen’s sex-specific effects on ischemic cell death and estrogen receptor mRNA expression in rat cortical organotypic explants

“…While ERβ mRNA does not significantly increase across time in cortical explants, it does follow similar trends to the intact cortex. As previously reported, AR mRNA was also not sexually dimorphic in the cortex across development [73] , [74] . However, to our knowledge, we are the first to report that increases in AR mRNA also occur in cortical explants, regardless of sex.…”

Time-restricted feeding alters lipid and amino acid metabolite rhythmicity without perturbing clock gene expression

“…Transcripts with a 12 h circadian period showed an enrichment for transcriptional activity, and for PI3K regulatory activity. Additionally, transcripts with differential rhythmicity were involved in RNA processing 35 – 37 and transcriptional regulation 38 – 40 , as well as PI3K/AKT signaling 41 . These findings corroborate results from rodent studies showing that fasted circadian sampling regulates skeletal and cardiac muscle anabolic signaling 27 .…”

Sex Differences in the Development of the Rodent Corticolimbic System

“…While early studies in rats found estrogen receptor expression to peak at postnatal day (P)7 in both sexes (O'Keefe and Handa, 1990;O'Keefe et al, 1995), studies that have selectively examined ERα report peak mRNA expression at P1 in mice (Mogi et al, 2015) and protein expression at P10 in rats (Solum and Handa, 2001). In the mouse hippocampus, one study reports ERβ mRNA levels to decrease from E17 to P7 in both sexes (Mogi et al, 2015), while others report them to remain relatively stable (Ivanova and Cordian, 2000;Tsai et al, 2015;Franklin et al, 2019). These inconsistencies may be due, in part, to variances in what subregions of the hippocampus were examined.…”

“…Indeed, one study showed that the CA1, CA3, and dentate gyrus subregions of the mouse hippocampus each exhibits differential fluctuations in ERβ protein levels from P0 to P21 (Zuloaga et al, 2014). Meanwhile, AR mRNA levels in both the male and female mouse hippocampus increase from as early as E11 (Young and Chang, 1998), and up until P21 (Mogi et al, 2015;Tsai et al, 2015;Franklin et al, 2019).…”