Oxytocin, But Not Oxytocin Receptor, is Regulated by Oestrogen Receptor β in the Female Mouse Hypothalamus

In the female rat, oestrogen receptor (ER) beta is colocalized with both oxytocin- and vasopressin-producing neurones in the paraventricular nucleus of the hypothalamus (PVN). In this study, we demonstrate that the same pattern of colocalization between ERbeta and oxytocin exists in the female mouse. Because this nucleus contains only a negligible quantity of ERalpha, it is likely that the oestrogen-dependent regulation of oxytocin and vasopressin synthesis in the PVN is mediated by ERbeta. Thus, we compared the effect of ovarian hormones on oxytocin and vasopressin mRNA expression in the PVN of wild-type (WT) and ERbeta knockout (betaERKO) mice. We also compared the effects of ovarian hormones on oxytocin receptor (OTR) expression in the medial amygdala (MeA) and ventromedial nucleus of the hypothalamus (VMN) in female WT and betaERKO mice. Ovariectomized mice underwent long-term treatment with oestradiol or oil. Progesterone was given concurrently on the final 7 days of treatment, and all mice were killed 48 h after the final progesterone injection. In the PVN, hormone treatment increased oxytocin mRNA expression in WT but not betaERKO females. These results suggest that ERbeta is necessary for the regulation of the expression of oxytocin in the PVN. Hormone treatment had no effect on vasopressin mRNA expression in the PVN, but significantly increased OTR binding in both the VMN and the MeA in both genotypes. Collectively, our data show region and peptide specific regulation by ERalpha and ERbeta in the mouse hypothalamus.