Wired for Reproduction: Organization and Development of Sexually Dimorphic Circuits in the Mammalian Forebrain
Abstract
▪ Abstract Mammalian reproduction depends on the coordinated expression of behavior with precisely timed physiological events that are fundamentally different in males and females. An improved understanding of the neuroanatomical relationships between sexually dimorphic parts of the forebrain has contributed to a significant paradigm shift in how functional neural systems are approached experimentally. This review focuses on the organization of interconnected limbic-hypothalamic pathways that participate in the neural control of reproduction and summarizes what is known about the developmental neurobiology of these pathways. Sex steroid hormones such as estrogen and testosterone have much in common with neurotrophins and regulate cell death, neuronal migration, neurogenesis, and neurotransmitter plasticity. In addition, these hormones direct formation of sexually dimorphic circuits by influencing axonal guidance and synaptogenesis. The signaling events underlying the developmental activities of sex steroids involve interactions between nuclear hormone receptors and other transcriptional regulators, as well as interactions at multiple levels with neurotrophin and neurotransmitter signal transduction pathways.
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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 [61]
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- Authors
- Simerly, R. B.
- Affiliations
- Oregon Health & Science University (US)
- Corresponding author
- Simerly, Richard B.
- ORCID
- Simerly, Richard B.
- Venue
- Annual Review of Neuroscience
- Publisher
- Annual Reviews
- Published
- 2002-03
- Volume
- 25
- Issue
- 1
- Pages
- 507-536
- ISSN
- 0147-006X (ISSN-L)
- 1545-4126
- OpenAlex
- W2144727302
- Cited by
- 723
- References
- 3
- Citations by year
- 2026: 15 · 2025: 25 · 2024: 14 · 2023: 27 · 2022: 23 · 2021: 23 · 2020: 23 · 2019: 18 · 2018: 30 · 2017: 23 · 2016: 38 · 2015: 24 · 2014: 37 · 2013: 36 · 2012: 38
- FWCI
- 1.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK055819, DK 55819)
- National Institute of Neurological Disorders and Stroke (NS37952, R01NS037952)
- National Center for Research Resources (RR-00163.)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- sexual dimorphism, forebrain, sex hormones, estrogen, testosterone, neurotrophins, neuronal migration, neurogenesis, axon guidance, synaptogenesis, nuclear receptors, transcriptional regulation, neuronal development, reproductive behavior
- MeSH terms
- Animals, Cell Differentiation, Genes, Regulator, Humans, Nerve Growth Factors, Neural Pathways, Neuronal Plasticity, Reproduction, Sex Characteristics, Gonadal Steroid Hormones, Signal Transduction, Prosencephalon
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