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Involvement of ERalpha and ERbeta in estradiol-induced enhancement of hippocampal neurogenesis and sexual behaviour Mazzucco, Christine Anne


In this study we investigated the involvement of estrogen receptors alpha and beta in both sexual behaviour and estradiol-induced enhancement of hippocampal neurogenesis in the adult female rat. Our study utilized recently available subtype selective alpha and beta estrogen receptor (ER) agonists, propyl-pyrazole triol (PPT) and diarylpropionitrile (DPN) to examine each receptor's contribution, individual and co-operative, for these primarily estradiol-mediated processes. To evaluate sexual behaviour and cell proliferation, rats were bi-laterally ovariectomized (OVX) and received subcutaneous injections of estradiol (10 (ag), PPT and DPN alone (1.25, 2.5, 5.0 mg /0.1 ml DMSO) or in combination (2.5 mg PPT + 2.5 mg DPN/ 0.1 ml DMSO). For experiment 1, our findings demonstrate that ERalpha is involved in eliciting both proceptive and receptive behaviour. Our laboratory has previously found that estradiol increases cell proliferation within 4 hrs in the dentate gyrus of adult female rats, therefore, for experiment 2 we administered estradiol or the agonist(s) 4 hrs prior to the cell synthesis marker bromodeoxyuridine (BrdU; 200 mg/kg). DPN enhanced cell proliferation by approximately 40% at all three administered doses (1.25 mg, p<0.008; 2.5 mg, p<0.003; 5 mg, p< 0.005), whereas PPT showed increased cell proliferation (by approximately 50%, p< 0.0002) at a specific dose of 2.5 mg. Our results demonstrate both ERalpha and ERbeta are individually involved in estradiol-enhanced cell proliferation. Dual receptor activation resulted in decreased levels of proceptivity, receptivity and cell proliferation, compared to either agonist alone, supporting previous studies suggesting that ERalpha and ERbeta may modulate each other's activity. Our results demonstrate the exclusive involvement of each ER subtype in two distinct physiological processes, sexual behaviour and hippocampal cell proliferation and suggest that a component of ER regulated cell proliferation may take place through alternative ligand and/or cell-signaling mechanisms.

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