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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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Gene expression in the BNSTp of WT and ARKO mice on ED18 and PD4.The mRNA levels of AR (A), aromatase (B), ERα (C), and ERβ (D) were normalized to the amount of total RNA. The number in each column indicates the number of animals used in the experiments. Values (mean ± SEM) with different letters differ significantly (p<0.05). *, p<0.05 vs. WT male mice on PD4. ND, not detected. AR mRNA levels in one WT male and one WT female were almost undetectable on ED18 (data not shown).
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pone-0112616-g006: Gene expression in the BNSTp of WT and ARKO mice on ED18 and PD4.The mRNA levels of AR (A), aromatase (B), ERα (C), and ERβ (D) were normalized to the amount of total RNA. The number in each column indicates the number of animals used in the experiments. Values (mean ± SEM) with different letters differ significantly (p<0.05). *, p<0.05 vs. WT male mice on PD4. ND, not detected. AR mRNA levels in one WT male and one WT female were almost undetectable on ED18 (data not shown).

Mentions: In addition to the AVPV of ARKO mice, the AR mRNA level was undetectable in the BNSTp of ARKO mice (Figure 6A). AR mRNA levels in the BNSTp of WT mice were also undetectable on ED18, except in one mouse for each sex, in which the AR mRNA level was close to the least detectable level (data not shown). Conversely, on PD4, the BNSTp of WT mice in both sexes expressed AR mRNA at a high level without a sex difference. In terms of aromatase, ERα, and ERβ, their mRNA expression was completely different between the BNSTp and AVPV in perinatal mice. In the BNSTp, aromatase mRNA levels were significantly increased on PD4 by AR gene deletion (Figure 6B). Specifically, when compared between WT and ARKO mice of each sex, aromatase mRNA levels in the BNSTp of ARKO male mice were significantly higher than those of WT male mice on PD4, but no significant difference was found between WT and ARKO female mice. Age-difference patterns and effects of AR gene deletion on ERα mRNA expression in the BNSTp were the same as those of aromatase mRNA expression. ERα mRNA levels in the BNSTp were significantly increased on PD4 by AR gene deletion, which was mainly due to a significant increase in ARKO male mice (Figure 6C). ERβ mRNA was detected in the BNSTp on ED18 and PD4, although it was not detected in the AVPV on the same days. The mRNA levels of ERβ in the BNSTp of WT and ARKO mice were significantly higher on PD4 than those on ED18 (Figure 6D). In addition, ERβ mRNA levels in the BNSTp on PD4 were significantly higher in ARKO mice than those in WT mice. Thus, the patterns of aromatase, ERα, and ERβ expression from ED18 to PD4 were different between the AVPV and BNSTp, and AR gene deletion caused significant changes in the expression of these genes in the BNSTp, but not the 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)

Gene expression in the BNSTp of WT and ARKO mice on ED18 and PD4.The mRNA levels of AR (A), aromatase (B), ERα (C), and ERβ (D) were normalized to the amount of total RNA. The number in each column indicates the number of animals used in the experiments. Values (mean ± SEM) with different letters differ significantly (p<0.05). *, p<0.05 vs. WT male mice on PD4. ND, not detected. AR mRNA levels in one WT male and one WT female were almost undetectable on ED18 (data not shown).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0112616-g006: Gene expression in the BNSTp of WT and ARKO mice on ED18 and PD4.The mRNA levels of AR (A), aromatase (B), ERα (C), and ERβ (D) were normalized to the amount of total RNA. The number in each column indicates the number of animals used in the experiments. Values (mean ± SEM) with different letters differ significantly (p<0.05). *, p<0.05 vs. WT male mice on PD4. ND, not detected. AR mRNA levels in one WT male and one WT female were almost undetectable on ED18 (data not shown).
Mentions: In addition to the AVPV of ARKO mice, the AR mRNA level was undetectable in the BNSTp of ARKO mice (Figure 6A). AR mRNA levels in the BNSTp of WT mice were also undetectable on ED18, except in one mouse for each sex, in which the AR mRNA level was close to the least detectable level (data not shown). Conversely, on PD4, the BNSTp of WT mice in both sexes expressed AR mRNA at a high level without a sex difference. In terms of aromatase, ERα, and ERβ, their mRNA expression was completely different between the BNSTp and AVPV in perinatal mice. In the BNSTp, aromatase mRNA levels were significantly increased on PD4 by AR gene deletion (Figure 6B). Specifically, when compared between WT and ARKO mice of each sex, aromatase mRNA levels in the BNSTp of ARKO male mice were significantly higher than those of WT male mice on PD4, but no significant difference was found between WT and ARKO female mice. Age-difference patterns and effects of AR gene deletion on ERα mRNA expression in the BNSTp were the same as those of aromatase mRNA expression. ERα mRNA levels in the BNSTp were significantly increased on PD4 by AR gene deletion, which was mainly due to a significant increase in ARKO male mice (Figure 6C). ERβ mRNA was detected in the BNSTp on ED18 and PD4, although it was not detected in the AVPV on the same days. The mRNA levels of ERβ in the BNSTp of WT and ARKO mice were significantly higher on PD4 than those on ED18 (Figure 6D). In addition, ERβ mRNA levels in the BNSTp on PD4 were significantly higher in ARKO mice than those in WT mice. Thus, the patterns of aromatase, ERα, and ERβ expression from ED18 to PD4 were different between the AVPV and BNSTp, and AR gene deletion caused significant changes in the expression of these genes in the BNSTp, but not the 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