Differential Control of Sex Differences in Estrogen Receptor α in the Bed Nucleus of the Stria Terminalis and Anteroventral Periventricular Nucleus

The principal nucleus of the bed nucleus of the stria terminalis (BNSTp) and anteroventral periventricular nucleus of the hypothalamus (AVPV) are sexually dimorphic, hormone-sensitive forebrain regions. Here we report a profound sex difference in estrogen receptor-alpha (ER alpha) immunoreactivity (IR) in the BNSTp, with robust ER alpha IR in females and the near absence of labeling in males. This sex difference is due to the suppression of ER alpha IR by testicular hormones in adulthood: it was not present at birth and was not altered by neonatal treatment of females with estradiol; gonadectomy of adult males increased ER alpha IR to that of females, whereas gonadectomy of adult females had no effect. Treating gonadally intact males with an aromatase inhibitor partially feminized ER alpha IR in the BNSTp, suggesting that testicular suppression required aromatization. By contrast, in AVPV we found a modest sex difference in ER alpha IR that was relatively insensitive to steroid manipulations in adulthood. ER alpha IR in AVPV was, however, masculinized in females treated with estradiol at birth, suggesting that the sex difference is due to organizational effects of estrogens. The difference in ER alpha IR in the BNSTp of males and females appears to be at least in part due to greater expression of mRNA of the ER alpha gene (Esr1) in females. The sex difference in message is smaller than the difference in immunoreactivity, however, suggesting that posttranscriptional mechanisms also contribute to the pronounced suppression of ER alpha IR and presumably to functions mediated by ER alpha in the male BNSTp.