Actions of Peripubertal Gonadal Steroids in the Formation of Sexually Dimorphic Brain Regions in Mice

Endocrinology. 2020 Jun 1;161(6):bqaa063. doi: 10.1210/endocr/bqaa063.


The calbindin-sexually dimorphic nucleus (CALB-SDN) and calbindin-principal nucleus of the bed nucleus of the stria terminalis (CALB-BNSTp) show male-biased sex differences in calbindin neuron number. The ventral part of the BNSTp (BNSTpv) exhibits female-biased sex differences in noncalbindin neuron number. We previously reported that prepubertal gonadectomy disrupts the masculinization of the CALB-SDN and CALB-BNSTp and the feminization of the BNSTpv. This study aimed to determine the action mechanisms of testicular androgens on the masculinization of the CALB-SDN and CALB-BNSTp and whether ovarian estrogens are the hormones that have significant actions in the feminization of the BNSTpv. We performed immunohistochemical analyses of calbindin and NeuN, a neuron marker, in male mice orchidectomized on postnatal day 20 (PD20) and treated with cholesterol, testosterone, estradiol, or dihydrotestosterone during PD20-70, female mice ovariectomized on PD20 and treated with cholesterol or estradiol during PD20-70, and PD70 mice gonadectomized on PD56. Calbindin neurons number in the CALB-SDN and CALB-BNSTp in males treated with testosterone or dihydrotestosterone, but not estradiol, was significantly larger than that in cholesterol-treated males. Noncalbindin neuron number in the BNSTpv in estradiol-treated females was significantly larger than that in cholesterol-treated females. Gonadectomy on PD56 had no significant effect on neuron numbers. Additionally, an immunohistochemical analysis revealed the expression of androgen receptors in the CALB-SDN and CALB-BNSTp of PD30 males and estrogen receptors-α in the BNSTpv of PD30 females. These results suggest that peripubertal testicular androgens act to masculinize the CALB-SDN and CALB-BNSTp without aromatization, and peripubertal ovarian estrogens act to feminize the BNSTpv.

Keywords: NeuN; calbindin; estradiol; puberty; sexually dimorphic nucleus; testosterone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / growth & development
  • Brain / metabolism*
  • Calbindins / metabolism
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism
  • Estrogens / metabolism
  • Female
  • Gonadal Steroid Hormones / metabolism*
  • Male
  • Mice / genetics
  • Mice / growth & development
  • Mice / metabolism*
  • Neurons / metabolism
  • Ovary / growth & development
  • Ovary / metabolism
  • Puberty / metabolism*
  • Sex Characteristics*
  • Testis / metabolism
  • Testosterone / metabolism


  • Calbindins
  • Estrogen Receptor alpha
  • Estrogens
  • Gonadal Steroid Hormones
  • Testosterone