Sexual Differentiation of the Vertebrate Brain: Principles and Mechanisms
Abstract
A wide variety of sexual dimorphisms, structural differences between the sexes, have been described in the brains of many vertebrate species, including humans. In animal models of neural sexual dimorphism, gonadal steroid hormones, specifically androgens, play a crucial role in engendering these differences by masculinizing the nervous system of males. Usually, the androgen must act early in life, often during the fetal period to masculinize the nervous system and behavior. However, there are a few examples of androgen, in adulthood, masculinizing both the structure of the nervous system and behavior. In the modal pattern, androgens are required both during development and adulthood to fully masculinize brain structure and behavior. In rodent models of neural sexual dimorphism, it is often the aromatized metabolites of androgen, i.e., estrogens, which interact with estrogen receptors to masculinize the brain, but there is little evidence that aromatized metabolites of androgen play this role in primates, including humans. There are other animal models where androgens themselves masculinize the nervous system through interaction with androgen receptors. In the course of masculinizing the nervous system, steroids can affect a wide variety of cellular mechanisms, including neurogenesis, cell death, cell migration, synapse formation, synapse elimination, and cell differentiation. In animal models, there are no known examples where only a single neural center displays sexual dimor…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In primates, much of sexual differentiation of the brain occurs in utero.
“By compar- ison, in primates much of this differentia- tion occurs in utero (Cooke et al. 1998).”
From Androgens and environmental antiandrogens affect reproductive development and play behavior in the Sprague-Dawley rat. (2002) · cites this paper as Cooke et al. 1998
Cites
PHOENIX, C. H., GOY, R. W., GERALL, A. A., & YOUNG, W. C. (1959) · Endocrinology · doi:10.1210/endo-65-3-369 · Cited by 1,934 · see citing works
Sex difference in the bed nucleus of the stria terminalis of the human brain
Allen, L. S., & Gorski, R. A. (1990) · Journal of Comparative Neurology · doi:10.1002/cne.903020402 · Cited by 281 · see citing works
Genetically Triggered Sexual Differentiation of Brain and Behavior
Arnold, A. P. (1996) · Hormones and Behavior · doi:10.1006/hbeh.1996.0053 · Cited by 141 · see citing works
Micevych, P., Akesson, T., & Elde, R. (1988) · Journal of Comparative Neurology · doi:10.1002/cne.902690306 · Cited by 104 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Pubertal hormones organize the adolescent brain and behavior
Sisk, C. L., & Zehr, J. L. (2005) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2005.10.003 · Cited by 1,082 · see citing works
Somerville, L. H., Jones, R. M., & Casey, B. J. (2010) · Brain and Cognition · doi:10.1016/j.bandc.2009.07.003 · Cited by 1,025 · see citing works
Abbott, D. H., Barnett, D. K., Bruns, C. M., & Dumesic, D. A. (2005) · Human Reproduction Update · doi:10.1093/humupd/dmi013 · Cited by 555 · see citing works
Estrogen, cognition and female ageing
Genazzani, A. R., Pluchino, N., Luisi, S., & Luisi, M. (2007) · Human Reproduction Update · doi:10.1093/humupd/dml042 · Cited by 237 · see citing works
Freeman, S. M., & Young, L. J. (2016) · Journal of Neuroendocrinology · doi:10.1111/jne.12382 · Cited by 196 · see citing works
“( B ) The olfactory information pathway in the rodent brain, including regions involved in social recognition (112,113).”
BackgroundCicero, T. J., Nock, B., O’Connor, L., & Meyer, E. R. (2002) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.300.2.695 · Cited by 150 · see citing works
Cao, J., Rebuli, M. E., Rogers, J., Todd, K. L., Leyrer, S. M., Ferguson, S. A., & Patisaul, H. B. (2013) · Toxicological Sciences · doi:10.1093/toxsci/kft035 · Cited by 141 · see citing works
Han, T. M., & De Vries, G. J. (2003) · Journal of Neurobiology · doi:10.1002/neu.10157 · Cited by 116 · see citing works
The emergence of gonadal hormone influences on dopaminergic function during puberty
Kuhn, C., Johnson, M., Thomae, A., Luo, B., Simon, S. A., Zhou, G., & Walker, Q. D. (2010) · Hormones and Behavior · doi:10.1016/j.yhbeh.2009.10.015 · Cited by 113 · see citing works
Coming of age in the Kisspeptin Era: Sex differences, development, and puberty
Kauffman, A. S. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.01.017 · Cited by 106 · see citing works
Pregnancy outcomes in women with congenital virilizing adrenal hyperplasia
Lo, J. C., & Grumbach, M. M. (2001) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(08)70027-6 · Cited by 98 · see citing works
Deussing, J. M., Breu, J., Kuhne, C., Kallnik, M., Bunck, M., Glasl, L., Yen, Y.-C., Schmidt, M. V., Zurmuhlen, R., Vogl, A. M., et al. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1049-10.2010 · Cited by 86 · see citing works
Arambula, S. E., Belcher, S. M., Planchart, A., Turner, S. D., & Patisaul, H. B. (2016) · Endocrinology · doi:10.1210/en.2016-1339 · Cited by 87 · see citing works
Hotchkiss, A. K., Ostby, J. S., Vandenburgh, J. G., & Gray, L. E. (2002) · Environmental Health Perspectives · doi:10.1289/ehp.02110s3435 · Cited by 82 · see citing works
“Although limited examples of androgen organization of behavior exist in the rat, it appears to be more common in the nonhuman primate (Cooke et al. 1998; Hines 1992).”
BackgroundCastellanos, M. C., Tang, J. C. Y., & Allan, D. W. (2013) · Development · doi:10.1242/dev.094714 · Cited by 65 · see citing works
Koshibu, K., Levitt, P., & Ahrens, E. T. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2004.03.051 · Cited by 62 · see citing works
Ferguson, S. A., Law, C. D., & Abshire, J. S. (2011) · Toxicological Sciences · doi:10.1093/toxsci/kfr201 · Cited by 54 · see citing works
Jessen, H. M., Kolodkin, M. H., Bychowski, M. E., Auger, C. J., & Auger, A. P. (2010) · Endocrinology · doi:10.1210/en.2009-0594 · Cited by 53 · see citing works
Viglietti-Panzica, C., Mura, E., & Panzica, G. (2007) · Hormones and Behavior · doi:10.1016/j.yhbeh.2006.12.003 · Cited by 37 · see citing works
Lonstein, J. S., Rood, B. D., & De Vries, G. J. (2005) · Endocrinology · doi:10.1210/en.2004-1315 · Cited by 33 · see citing works
- Authors
- Cooke, B., Hegstrom, C. D., Villeneuve, L. S., & Breedlove, S. M.
- Affiliations
- University of California, Berkeley (US)
- Venue
- Frontiers in Neuroendocrinology
- Publisher
- Elsevier BV
- Published
- 1998-10
- Volume
- 19
- Issue
- 4
- Pages
- 323-362
- ISSN
- 0091-3022 (ISSN-L)
- OpenAlex
- W2103948764
- Cited by
- 504
- References
- 4
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 12 · 2021: 29 · 2020: 15 · 2019: 3 · 2018: 20 · 2017: 10 · 2016: 20 · 2015: 9 · 2014: 17 · 2013: 22 · 2012: 20
- FWCI
- 4.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Frontiers in Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- sexual dimorphism, sexual differentiation of the brain, androgens, sex steroids, estrogen receptor, androgen receptor, aromatization, neurogenesis, synaptogenesis, sex differences in behavior, human brain, vertebrate brain
- MeSH terms
- Animals, Brain, Humans, Nervous System Physiological Phenomena, Sex Characteristics, Steroids, Vertebrates
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
