Sex steroids during developmental period are critical to
formation of sexually dimorphic nuclei in the brain, although the mechanisms of
sex-steroid actions
remain to be elucidated. 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 male mice than in female mice, involves aromatized
androgens that act 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 exhibits sex differences opposite to those
in BNSTp. Morphometrical
analysis of aromatase knockout (AromKO), ERα knockout (αERKO), and ERβ
knockout (βERKO) mice revealed
that the volume and neuron number of the AVPV in AromKO and αERKO male mice were significantly smaller than those
in wild-type males. We further examined
the AVPV and BNSTp of androgen receptor knockout (ARKO) mice. The volume and
neuron number of the BNSTp were significantly smaller in ARKO male mice than those
in wild-type mice. These effects were not rescued by neonatal treatment of aromatizable
testosterone. In contrast, there was no significant difference in the AVPV
between ARKO and wild-type mice. We also investigated aromatase, ERα, ERβ, and AR mRNA
levels in the AVPV and BNSTp of perinatal
mice. The AVPV and
BNSTp differed with regard to expression of each mRNA. These results suggested
that androgen signaling via AR and estrogen signaling via ERα are requisite for
masculinization of the BNSTp, whereas estrogen signaling via ERα is sufficient
for defeminization of the AVPV.