Abstract
Administration of 17β-estradiol (E2) has beneficial effects on cognitive function in peri- but not post-menopausal women, yet the molecular mechanisms underlying age-related changes in E2 action remain unclear. We propose that there is a biological switch in E2 action that occurs coincident with age and length of time after ovarian hormone depletion, and we hypothesized that age-dependent regulation of microRNAs (miRNAs) could be the molecular basis for that switch. Previously we showed that miRNAs are regulated by E2 in young compared to aged female rats. Here we tested whether increasing lengths of ovarian hormone deprivation in aged females altered E2 regulation of these mature miRNAs. In addition, we determined where along the miRNA biogenesis pathway E2 exerted its effects. Our results showed that age and increased lengths of ovarian hormone deprivation abolished the ability of E2 to regulate mature miRNA expression in the brain. Further, we show that E2 acted at specific points along the miRNA biogenesis pathway.
Highlights
The average life expectancy has increased over the past century due to better living conditions and medical advancements [1]
We propose that there is a biological switch in E2 action that occurs coincident with age and length of time after ovarian hormone depletion, and we hypothesized that age-dependent regulation of microRNAs could be the molecular basis for that switch
The levels continued to increase with age in ovarian intact animals, but this result was not observed in either OVX group (Figure 2b). miR-9: Similar to let-7i, we observed no changes in miR-9 expression across all time points in ovarian intact animals (Figure 2c), but there was a significant increase over time in OVX+veh animals. miR-9-3p: Interestingly, www.impactjournals.com/oncotarget
Summary
The average life expectancy has increased over the past century due to better living conditions and medical advancements [1]. ERα and ERβ display brain region specific expression patterns, and have dichotomous effects on brain function [47, 48] Both receptors have been shown to regulate miRNA expression in-vitro, it is not known whether one or both receptors are required for mediating E2-induced miRNA expression in the brain [49, 50]. Our previous work showed that E2 differentially regulated miRNA expression in the brain of young (3 mo.) compared to aged (18 mo.) female rats In this current study we extended those observations by investigating if longer periods of E2 deprivation in aged female rats altered the E2-dependent regulation of miRNAs we previously observed in the brain. Our results show that extended deprivation of ovarian hormones markedly alters E2 regulation of mature miRNAs in the aged female hypothalamus, suggesting that there is a shift in how the brain responds to the re-introduction of E2 after prolonged periods of ovarian hormone deprivation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
