Control of Cell Number in the Bed Nucleus of the Stria Terminalis of Mice: Role of Testosterone Metabolites and Estrogen Receptor Subtypes
Abstract
Introduction The bed nucleus of the stria terminalis (BNST) exhibits several sex differences that may be related to male sexual behavior and gender identity. In mice and rats, sex differences in the principal nucleus of the BNST (BNSTp) are due to sexually dimorphic cell death during perinatal life. Although testosterone treatment of newborn female rats increases BNSTp cell number, the relevant hormone metabolite(s) are not known, and the effect of testosterone on the development of BNSTp cell number in mice has not been examined. Aim To identify the sex hormone metabolites and receptors controlling cell number, volume, and cell size in the BNSTp of mice. Methods In the first experiment, C57BL/6J male mice were injected on the day of birth with peanut oil; females were injected with testosterone propionate (TP), estradiol benzoate (EB), dihydrotestosterone propionate (DHTP), or oil alone, and the BNSTp of all animals was examined in adulthood. In the second experiment, to compare effects of EB to the effects of estrogen receptor subtype specific agonists, newborn female mice were injected with EB, propyl-pyrazole-triol (PPT, a selective estrogen receptor alpha [ERalpha] agonist), or diarylpropionitrile (DPN, a selective estrogen receptor beta [ERbeta] agonist). Main outcome measures Nuclear volume measurements and stereological cell counts in the BNSTp in adulthood. Results TP treatment of newborn females completely masculinized both BNSTp volume and cell number. EB masculini…
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A single dose of testosterone propionate (100 μg) has been shown to masculinize a female rodent brain.
“Testosterone propionate (Sigma; 100μg in 20 μl sesame oil, a dose previously shown to induce brain masculinization in a female rodent) (Ghahramani et al., 2014; Goel and Bale, 2013; Hisasue et al., 2010; Nakachi et al., 2015; Seney et al., 2012)”
From Excess Neonatal Testosterone Causes Male-Specific Social and Fear Memory Deficits in Wild-Type Mice (2025) · cites this paper as Hisasue et al., 2010
The single moderate dose and timing of testosterone used in this study has been shown to masculinize a female rodent brain.
“This dose and timing was chosen because it has been shown to masculinize a female rodent brain”
From Excess Neonatal Testosterone Causes Male-Specific Social and Fear Memory Deficits in Wild-Type Mice (2025) · cites this paper as Hisasue et al., 2010
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Sex differences in mood disorders: Perspectives from humans and rodent models
Seney, M. L., & Sibille, E. (2014) · Biology of Sex Differences · doi:10.1186/s13293-014-0017-3 · Cited by 181 · see citing works
Self-citationExcess Neonatal Testosterone Causes Male-Specific Social and Fear Memory Deficits in Wild-Type Mice
Quiñones-Labernik, P., Blocklinger, K. L., Bruce, M. R., Hagan, E., Preuschl, D., Tesar, C., & Ferri, S. L. (2025) · eneuro · doi:10.1523/eneuro.0020-25.2025 · Cited by 4 · see citing works
- Authors
- Hisasue, S.-I., Seney, M. L., Immerman, E., & Forger, N. G.
- Affiliations
- Sapporo Medical University (JP)
- University of Massachusetts Amherst (US)
- Corresponding author
- Hisasue, Shin-ichi
- Venue
- The Journal of Sexual Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-04-01
- Volume
- 7
- Issue
- 4_Part_1
- Pages
- 1401-1409
- ISSN
- 1743-6095 (ISSN-L)
- 1743-6109
- OpenAlex
- W2145632985
- Cited by
- 78
- References
- 7
- Citations by year
- 2026: 1 · 2025: 5 · 2023: 9 · 2022: 2 · 2021: 1 · 2020: 6 · 2019: 7 · 2018: 3 · 2017: 7 · 2016: 5 · 2015: 2 · 2014: 8 · 2013: 11 · 2012: 5
- FWCI
- 2.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Journal of Sexual Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (K02MH072825, R01MH068482)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- bed nucleus of the stria terminalis, testosterone metabolites, estradiol benzoate, dihydrotestosterone, estrogen receptor alpha, estrogen receptor beta, masculinization, cell number, nuclear volume, perinatal hormone exposure, sex differences in brain development
- MeSH terms
- Animals, Animals, Newborn, Cell Count, Estradiol, Female, Injections, Subcutaneous, Male, Mice, Inbred C57BL, Nitriles, Phenols, Propionates, Pyrazoles, Septal Nuclei, Sex Differentiation, Dihydrotestosterone, Testosterone Propionate, Estrogen Receptor alpha, Estrogen Receptor beta, Cell Size, Mice
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