Effects of oral estrogen, raloxifene and arzoxifene on gene expression in serotonin neurons of macaques

摘要: The serotonin neural system contributes to cognition and affect, both of which exhibit pathologies with gender bias. We previously showed that estrogen (E) treatment female macaques via Silastic implant alters gene expression for tryptophan hydroxylase (TPH), the reuptake transporter (SERT) 5HT1A autoreceptor. In addition, we have found neurons express ER beta (ERβ). Together these studies suggest could transduce action ERβ on aspects mood cognition. However, replacement therapy can increase risk breast uterine cancer. Therefore, questioned whether selective receptor modulators, raloxifene arzoxifene, act in a manner similar E nonhuman primate model. Female rhesus were ovariectomized orally dosed vehicle, estradiol 17β, or arzoxifene once per day by sipper bottles 30 days. animals then euthanized midbrains prepared situ hybridization TPH, SERT mRNAs followed densitometric analysis. There was significant TPH total signal (positive pixels×OD) E, respectively. decrease mRNA optical density all treatments. autoreceptor did not change any treatment. If changes are reflected functional proteins, neurotransmission little no negative peripheral tissues. conclusion, natural neurons. This suggests agonists at context neuron. responses more variable less robust oral dosing paradigm compared chronic paradigm.