PMID- 25398007 OWN - NLM STAT- MEDLINE DCOM- 20151230 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 11 DP - 2014 TI - 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. PG - e112616 LID - 10.1371/journal.pone.0112616 [doi] LID - e112616 AB - 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-alpha (ERalpha), but not estrogen receptor-beta (ERbeta). 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, ERalpha, or ERbeta genes revealed that the volume and neuron number of the male AVPV were significantly increased by deletion of aromatase and ERalpha genes, but not the ERbeta 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, ERalpha, 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 ERalpha mRNA level was higher on PD4 without any effect of AR gene deletion. Aromatase and ERalpha mRNA levels in the male BNSTp were significantly increased on PD4 by AR gene deletion. These results suggest that estradiol signaling via ERalpha 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. FAU - Kanaya, Moeko AU - Kanaya M AD - Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama, Japan. FAU - Tsuda, Mumeko C AU - Tsuda MC AD - Laboratory of Behavioral Neuroendocrinology, University of Tsukuba, Tsukuba, Japan. FAU - Sagoshi, Shoko AU - Sagoshi S AD - Laboratory of Behavioral Neuroendocrinology, University of Tsukuba, Tsukuba, Japan. FAU - Nagata, Kazuyo AU - Nagata K AD - Laboratory of Behavioral Neuroendocrinology, University of Tsukuba, Tsukuba, Japan. FAU - Morimoto, Chihiro AU - Morimoto C AD - Laboratory of Behavioral Neuroendocrinology, University of Tsukuba, Tsukuba, Japan. FAU - Thu, Chaw Kyi Tha AU - Thu CK AD - Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama, Japan. FAU - Toda, Katsumi AU - Toda K AD - Department of Biochemistry, School of Medicine, Kochi University, Nankoku, Japan. FAU - Kato, Shigeaki AU - Kato S AD - Soma Central Hospital, Fukushima, Japan. FAU - Ogawa, Sonoko AU - Ogawa S AD - Laboratory of Behavioral Neuroendocrinology, University of Tsukuba, Tsukuba, Japan. FAU - Tsukahara, Shinji AU - Tsukahara S AD - Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141114 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (DNA Primers) RN - 0 (Estrogen Receptor alpha) RN - 0 (Receptors, Androgen) RN - 3XMK78S47O (Testosterone) RN - EC 1.14.14.1 (Aromatase) SB - IM MH - Analysis of Variance MH - Animals MH - Aromatase/metabolism MH - Body Weights and Measures MH - DNA Primers/genetics MH - Estrogen Receptor alpha/*metabolism MH - Female MH - Gene Expression Profiling MH - Hypothalamus, Anterior/*embryology/*metabolism MH - Male MH - Mice MH - Mice, Knockout MH - Receptors, Androgen/genetics MH - Septal Nuclei/*embryology/*metabolism MH - *Sex Characteristics MH - Testosterone/*metabolism PMC - PMC4232352 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/11/15 06:00 MHDA- 2015/12/31 06:00 PMCR- 2014/11/14 CRDT- 2014/11/15 06:00 PHST- 2014/06/10 00:00 [received] PHST- 2014/10/02 00:00 [accepted] PHST- 2014/11/15 06:00 [entrez] PHST- 2014/11/15 06:00 [pubmed] PHST- 2015/12/31 06:00 [medline] PHST- 2014/11/14 00:00 [pmc-release] AID - PONE-D-14-25651 [pii] AID - 10.1371/journal.pone.0112616 [doi] PST - epublish SO - PLoS One. 2014 Nov 14;9(11):e112616. doi: 10.1371/journal.pone.0112616. eCollection 2014.