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Abstract :
[en] Nuclear receptors such as the estrogen receptors (ER) require the presence of coactivator
proteins, such as the steroid receptor coactivator (SRC-1) and coactivator-associated arginine
methyltransferase (CARM1) to enhance the transcription of target genes. Importantly, in vitro work
suggests that ER and ER differ in the ability to recruit coactivators such as SRC-1. For example, SRC-1
has a strong affinity for ER and a weaker affinity for ER. Interestingly, both ER and ER are
individually involved in estradiol-enhanced cell proliferation in the dentate gyrus of adult female rats. In
addition, previous work suggests a role for CARM1 in cell proliferation and for SRC-1 in cell
differentiation, therefore the present study aimed to determine whether proliferating cells in the dentate
gyrus of the hippocampus co-express the coactivators SRC-1 and CARM1. We also aimed to determine
whether ER and ER agonists would result in altered expression of SRC-1 and CARM1 in new
proliferating cells in the dentate gyrus. To investigate this, adult female rats were ovariectomized and
treated with either the ER agonist Propyl-pyrazole triol (PPT), the ER agonist diarylpropionitrile
(DPN), estradiol benzoate (EB), or vehicle (CTRL). Rats were then injected with BrdU (200 mg/kg) and
sacrificed 24 hours later. Preliminary data suggests that DPN, PPT and EB increase cell proliferation in the
dentate gyrus compared to the vehicle-injected group. Interestingly, the number of proliferating cell
expressing SRC-1 is similar in all groups, suggesting that neither of the ER agonists nor EB treatment
affects the co-expression of BrdU+ cells with SRC-1. However, additional measurements are currently
being done to investigate whether CARM-1 is differentially expressed in proliferating cells in the
hippocampus following selective ER agonist treatment.