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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.

Kanaya M, Tsuda MC, Sagoshi S, Nagata K, Morimoto C, Thu CK, Toda K, Kato S, Ogawa S, Tsukahara S - PLoS ONE (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama, Japan.

ABSTRACT
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.

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Effects of AR gene deletion on the BNSTp.Photomicrographs (A) show the BNSTp in WT and ARKO mice of both sexes. Dotted lines indicate border areas of the BNSTp. Scale bars indicate 200 µm. f, fornix; sm, stria medullaris of thalamus; 3V, third ventricle. The volume (B) and neuronal cell number (C) in the BNSTp of WT and ARKO mice. The volume (D) and neuronal cell number (E) in the BNSTp of WT and ARKO male mice that were treated with TP or sesame oil (vehicle) on the day of birth. See Figure 2 for details.
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pone-0112616-g003: Effects of AR gene deletion on the BNSTp.Photomicrographs (A) show the BNSTp in WT and ARKO mice of both sexes. Dotted lines indicate border areas of the BNSTp. Scale bars indicate 200 µm. f, fornix; sm, stria medullaris of thalamus; 3V, third ventricle. The volume (B) and neuronal cell number (C) in the BNSTp of WT and ARKO mice. The volume (D) and neuronal cell number (E) in the BNSTp of WT and ARKO male mice that were treated with TP or sesame oil (vehicle) on the day of birth. See Figure 2 for details.

Mentions: Although the morphology of the AVPV did not change in mice lacking the AR gene, the BNSTp was affected by AR gene deletion. The size of the BNSTp in ARKO male mice, but not ARKO female mice, was significantly smaller than that in WT littermates of the same sex (Figure 3A and 3B). The neuron number of the BNSTp in ARKO males was also significantly lower than that in WT males, and was comparable to that in WT and ARKO females (Figure 3C). The density of neurons and the number and density of glial cells in the BNSTp were not affected by deletion of the AR gene and did not differ between sexes (Table S5). Thus, morphometrical analyses of ARKO male mice indicated that there was a regional difference in the effects of the AR gene deletion between the AVPV and BNSTp. AR gene deletion increased the volume and neuron number of the male BNSTp, but did not affect those of the male AVPV.


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.

Kanaya M, Tsuda MC, Sagoshi S, Nagata K, Morimoto C, Thu CK, Toda K, Kato S, Ogawa S, Tsukahara S - PLoS ONE (2014)

Effects of AR gene deletion on the BNSTp.Photomicrographs (A) show the BNSTp in WT and ARKO mice of both sexes. Dotted lines indicate border areas of the BNSTp. Scale bars indicate 200 µm. f, fornix; sm, stria medullaris of thalamus; 3V, third ventricle. The volume (B) and neuronal cell number (C) in the BNSTp of WT and ARKO mice. The volume (D) and neuronal cell number (E) in the BNSTp of WT and ARKO male mice that were treated with TP or sesame oil (vehicle) on the day of birth. See Figure 2 for details.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232352&req=5

pone-0112616-g003: Effects of AR gene deletion on the BNSTp.Photomicrographs (A) show the BNSTp in WT and ARKO mice of both sexes. Dotted lines indicate border areas of the BNSTp. Scale bars indicate 200 µm. f, fornix; sm, stria medullaris of thalamus; 3V, third ventricle. The volume (B) and neuronal cell number (C) in the BNSTp of WT and ARKO mice. The volume (D) and neuronal cell number (E) in the BNSTp of WT and ARKO male mice that were treated with TP or sesame oil (vehicle) on the day of birth. See Figure 2 for details.
Mentions: Although the morphology of the AVPV did not change in mice lacking the AR gene, the BNSTp was affected by AR gene deletion. The size of the BNSTp in ARKO male mice, but not ARKO female mice, was significantly smaller than that in WT littermates of the same sex (Figure 3A and 3B). The neuron number of the BNSTp in ARKO males was also significantly lower than that in WT males, and was comparable to that in WT and ARKO females (Figure 3C). The density of neurons and the number and density of glial cells in the BNSTp were not affected by deletion of the AR gene and did not differ between sexes (Table S5). Thus, morphometrical analyses of ARKO male mice indicated that there was a regional difference in the effects of the AR gene deletion between the AVPV and BNSTp. AR gene deletion increased the volume and neuron number of the male BNSTp, but did not affect those of the male AVPV.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama, Japan.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus