Data from: Regional difference in sex steroid action on formation of morphological sex differences in the anteroventral periventricular nucleus and principal nucleus of the bed nucleus of the stria terminalis

Sex steroid action is critical to form sexually dimorphic nuclei, although it is not fully understood. We previously reported that masculinization of the principal nucleus of the bed nucleus of the stria terminalis (BNSTp), which is larger and has more neurons in males than in females, involves aromatized testosterone that acts via estrogen receptor-α (ERα), but not estrogen receptor-β (ERβ). Here, we examined sex steroid action on the formation of the anteroventral periventricular nucleus (AVPV) that is larger and has more neurons in females. Morphometrical analysis of transgenic mice lacking aromatase, ERα, or ERβ genes revealed that the volume and neuron number of the male AVPV were significantly increased by deletion of aromatase and ERα genes, but not the ERβ gene. We further examined the AVPV and BNSTp of androgen receptor knockout (ARKO) mice. The volume and neuron number of the male BNSTp were smaller in ARKO mice than those in wild-type mice, while no significant effect of ARKO was found on the AVPV and female BNSTp. We also examined aromatase, ERα, and AR mRNA levels in the AVPV and BNSTp of wild-type and ARKO mice on embryonic day (ED) 18 and postnatal day (PD) 4. AR mRNA in the BNSTp and AVPV of wild-type mice was not expressed on ED18 and emerged on PD4. In the AVPV, the aromatase mRNA level was higher on ED18, although the ERα mRNA level was higher on PD4 without any effect of AR gene deletion. Aromatase and ERα mRNA levels in the male BNSTp were significantly increased on PD4 by AR gene deletion. These results suggest that estradiol signaling via ERα during the perinatal period and testosterone signaling via AR during the postnatal period are required for masculinization of the BNSTp, whereas the former is sufficient to defeminize the AVPV.性激素的作用对于性二态性核团的形成至关重要，但其具体调控机制尚未完全阐明。我们此前的研究表明，终纹床核主核（principal nucleus of the bed nucleus of the stria terminalis, BNSTp）的雄性化——该核团在雄性个体中体积更大、神经元数量多于雌性——依赖于通过雌激素受体α（ERα）而非雌激素受体β（ERβ）发挥作用的芳香化睾酮。本研究针对前腹侧室周核（anteroventral periventricular nucleus, AVPV）的形成过程探究性激素的作用，该核团在雌性个体中体积更大、神经元数量更多。我们对缺失芳香化酶、ERα或ERβ基因的转基因小鼠进行形态计量分析，结果显示，敲除芳香化酶与ERα基因可显著增加雄性AVPV的体积与神经元数量，而敲除ERβ基因则无此效应。我们进一步检测了雄激素受体敲除（androgen receptor knockout, ARKO）小鼠的AVPV与BNSTp：雄性ARKO小鼠的BNSTp体积与神经元数量较野生型小鼠显著降低，而ARKO对AVPV以及雌性小鼠的BNSTp无明显影响。我们还检测了野生型与ARKO小鼠在胚胎日18（ED18）与出生后日4（PD4）时，AVPV与BNSTp中芳香化酶、ERα及雄激素受体（AR）的mRNA表达水平。野生型小鼠的BNSTp与AVPV中，AR mRNA在ED18时未表达，于PD4时开始表达。在AVPV中，芳香化酶mRNA在ED18时表达水平更高，而ERα mRNA在PD4时表达水平更高，且AR基因敲除对此无影响。雄性BNSTp中的芳香化酶与ERα mRNA水平在PD4时因AR基因敲除而显著升高。上述结果表明，围产期通过ERα介导的雌二醇信号通路，以及出生后通过AR介导的睾酮信号通路，是BNSTp雄性化所必需的；而前者足以实现AVPV的去雌性化。