Estrogen receptor-beta regulates transcript levels for oxytocin and arginine vasopressin in the hypothalamic paraventricular nucleus of male mice.

Estrogen receptor (ER)-beta, unlike ER-alpha, is localized in the hypothalamic paraventricular nucleus (PVN) which also contains neuropeptide synthesizing neurons, such as oxytocin (OT), arginine vasopressin (AVP) and corticotropin-releasing hormone (CRH). Although it is known that some ER-beta containing neurons co-express OT and AVP, but not CRH, in the PVN, it is not yet determined whether ER-beta activation may indeed play a role in estrogenic regulation on syntheses of these neuropeptides. In the present study, we tested this hypothesis by comparing the effects of estrogen on the levels of OT, AVP and CRH messenger RNA (mRNA) between ER-beta knockout (betaERKO) and wild type (WT) control male mice. Mice were gonadectomized and implanted with either a pellet containing estradiol benzoate (2.5-5.0 microg/day) or a placebo pellet for 21 days. In situ hybridization histochemistry revealed that estrogen treatment resulted in a significant increase in OT transcripts (151.6+/-6.0%) and a decrease in AVP transcripts (77.8+/-5.2%) in the PVN of WT mice, compared to the placebo control group. This estrogenic regulation of OT and AVP mRNA levels in the PVN was completely abolished in betaERKO mice. Similar genotype differences in the effects of estrogen on the numbers of OT- and AVP-containing cells were found in immunocytochemical studies performed in a separate set of mice. On the other hand, the expression of CRH mRNA in the PVN was not affected by estrogen treatment in either WT or betaERKO mice. Furthermore, estrogen did not cause any changes in the levels of OT or AVP mRNA, regardless of genotype, in the supraoptic nucleus where, unlike in rats, ER-beta containing neurons are rarely found in mice. Finally, estrogen significantly increased OT mRNA levels in both betaERKO and WT in the medial preoptic area, which contains both ER-alpha and ER-beta. These results suggest that ER-beta activation may play a critical role in estrogenic regulation of OT and AVP gene expression in the PVN.