Sexual differentiation of the rodent hypothalamus: Hormonal and environmental influences
Abstract
Brain sexual differentiation is a complex developmental phenomenon influenced by the genetic background, sex hormone secretions and environmental inputs, including pollution. The main hormonal drive to masculinize and defeminize the rodent brain is testosterone secreted by the testis. The hormone does not influence sex brain differentiation only in its native configuration, but it mostly needs local conversion into active metabolites (estradiol and DHT) through the action of specific enzymatic systems: the aromatase and 5alpha-reductase (5alpha-R), respectively. This allows the hormone to control target cell gene expression either through the estrogen (ER) or the androgen (AR) receptors. The developmental profile of testosterone metabolizing enzymes, different in the two sexes, is therefore of the utmost importance in affecting the bioavailability of the steroids active in brain differentiation. Widely diffused pollutants, like polychlorinated biphenyls (PCBs) are able to affect the production and/or action of testosterone metabolites, exerting detrimental influences on reproduction and sex behavior. The main studies performed in our and other laboratories concerning the pattern of expression and the control of the enzymatic systems involved in brain androgen action and metabolism are shortly reviewed. Some recent data on the influence exerted by PCBs on these metabolic systems are also reported.
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If the brain is exposed to testosterone either from its own testes in males or from an exogenous source in females, it will be masculinized.
“If the brain is exposed to testosterone either from its own testes in males or from an exogenous source in females, it will be masculinized [59–64].”
From Sex differences in metabolic homeostasis, diabetes, and obesity (2015) · cites this paper as [63]
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Sosa, C., Zapata, L. E. C., Cisternas, C. D., Arévalo, M., & Cambiasso, M. J. (2026) · Biology of Sex Differences · doi:10.1186/s13293-026-00854-4 · Cited by 1 · see citing works
Peruffo, A., Giacomello, M., Montelli, S., Panin, M., & Cozzi, B. (2013) · Neuroscience Letters · doi:10.1016/j.neulet.2013.10.026 · Cited by 1 · see citing works
Aromatase in human physiology and pathology: implications of human aromatase deficiency
Saraco, N. I., Costanzo, M., Guercio, G., Marino, R. M., Berensztein, E. B., Baquedano, M. S., & Belgorosky, A. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-821424-4.00028-9 · Cited by 1 · see citing works
Engineered Nuclear Hormone Receptor-Biosensors for Environmental Monitoring and Early Drug Discovery
Gierach, I., & Woo, D. (2011) · InTech eBooks · doi:10.5772/16374 · Cited by 1 · see citing works
Progranulin in Sexual Differentiation of the Developing Brain
Suzuki, M. (2019) · Springer eBooks · doi:10.1007/978-981-13-6186-9_6
- Authors
- Negri-Cesi, P., Colciago, A., Pravettoni, A., Casati, L., Conti, L., & Celotti, F.
- Affiliations
- University of Milan (IT)
- Venue
- The Journal of Steroid Biochemistry and Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 109
- Issue
- 3-5
- Pages
- 294-299
- ISSN
- 0960-0760 (ISSN-L)
- OpenAlex
- W2028297115
- Cited by
- 50
- References
- 58
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 4 · 2014: 1 · 2013: 4 · 2012: 4
- FWCI
- 0.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Iris (University of Trento) (submittedVersion)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Keywords
- sexual differentiation of the brain, hypothalamus, rodent brain, testosterone, aromatase, 5α-reductase, estradiol, dihydrotestosterone, androgen receptor, estrogen receptor, polychlorinated biphenyls, environmental pollutants, brain masculinization, sex hormones, reproductive toxicity, sexual behavior
- MeSH terms
- Animals, Environment, Environmental Pollutants, Hormones, Humans, Hypothalamus, Rodentia, Sex Differentiation
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