Gonadal Hormone–Dependent Sexual Differentiation of a Female-Biased Sexually Dimorphic Cell Group in the Principal Nucleus of the Bed Nucleus of the Stria Terminalis in Mice

Abstract

We recently reported a female-biased sexually dimorphic area in the mouse brain in the boundary region between the preoptic area and the bed nucleus of the stria terminalis (BNST). We reexamined this area and found that it is a ventral part of the principal nucleus of the BNST (BNSTp). The BNSTp is a male-biased sexually dimorphic nucleus, but the ventral part of the BNSTp (BNSTpv) exhibits female-biased sex differences in volume and neuron number. The volume and neuron number of the BNSTpv were increased in males by neonatal orchiectomy and decreased in females by treatment with testosterone, dihydrotestosterone, or estradiol within 5 days after birth. Sex differences in the volume and neuron number of the BNSTpv emerged before puberty. These sex differences became prominent in adulthood with increasing volume in females and loss of neurons in males during the pubertal/adolescent period. Prepubertal orchiectomy did not affect the BNSTpv, although prepubertal ovariectomy reduced the volume increase and induced loss of neurons in the female BNSTpv. In contrast, the volume and neuron number of male-biased sexually dimorphic nuclei that are composed of mainly calbindin neurons and are located in the preoptic area and BNST were decreased by prepubertal orchiectomy but not affected by prepubertal ovariectomy. Testicular testosterone during the postnatal period may defeminize the BNSTpv via binding directly to the androgen receptor and indirectly to the estrogen receptor after aromatization, although defeminization may proceed independently of testicular hormones in the pubertal/adolescent period. Ovarian hormones may act to feminize the BNSTpv during the pubertal/adolescent period.

Estrogenic regulation of social behavior and sexually dimorphic brain formation

“…Thus, CALB-D28K is useful to determine not only the CALB-SDN but also the CALB-BNSTp, although the physiological roles of CALB-D28K in the CALB-SDN and CALB-BNSTp require further investigation. The volume of the CALB-SDN and CALB-BNSTp are increased in adult female mice by postnatal treatment with testosterone propionate and EB, but not dihydrotestosterone, a non-aromatizable testosterone (Morishita et al, 2017;Orikasa and Sakuma, 2010), suggesting that postnatal testicular testosterone is aromatized and then acts via binding to ER for masculinization of the CALB-SDN and CALB-BNSTp.…”

“…CALB-D28K is therefore used as a marker to identify a sexually dimorphic nucleus that is included in the SDN-POA and was termed the CALB-SDN ( Figure 3). Like the SDN-POA, the BNSTp contains many CALB-D28K neurons, and the number of CALB-D28K neurons in the BNSTp is larger in males than in females (Gilmore et al, 2012;Morishita et al, 2017). Hereafter the BNSTp identified by CALB-D28K is termed CALB-BNSTp ( Figure 3).…”

“…In the CALB-SDN and CALB-BNSTp, the sex differences in the volume and numbers of CALB-D28K neurons emerge before puberty (Morishita et al, 2017;Wittmann and McLennan, 2013a, b). The sex…”

Anxious to see you: Neuroendocrine mechanisms of social vigilance and anxiety during adolescence

“…Consistent with this idea, work in mice shows that in both males and females, gonadal hormones modulate the size and chemoarchitecture of the posterior BNST during puberty (Morishita et al, 2017). It is unknown whether any of these sex differences contribute to social vigilance or anxiety.…”

“…Knowledge of BNST structure and function during adolescent development is sparse. Several subregions of the BNST are larger in males compared with females (Allen & Gorski, 1990;Campi, Jameson, & Trainor, 2013;Morishita, Maejima, & Tsukahara, 2017), and some show sex differences in chemoarchitecture (Bamshad, Novak, & Devries, 1993;Gegenhuber & Tollkuhn, 2019;Juntti et al, 2010). These sex differences in the neuroanatomy likely contribute to sex-dependent reproductive behaviors (Juntti et al, 2010) and learning patterns (Bangasser, Santollo, & Shors, 2005;Bangasser & Shors, 2008).…”