Regular Article
Sexual Differentiation of the Vertebrate Brain: Principles and Mechanisms,☆☆

https://doi.org/10.1006/frne.1998.0171Get rights and content

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 dimorphism. Rather, each case of sexual dimorphism seems to be part of a distributed network of sexually dimorphic neuronal populations which normally interact with each other. Finally, there is ample evidence of sexual dimorphism in the human brain, as sex differences in behavior would require, but there has not yet been any definitive proof that steroids acting early in development directly masculinize the human brain.

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      Based on our gene ontology analysis, we speculate that such dimorphisms most often differentially regulate synaptic architecture, transmission, or plasticity; response to extracellular signals; neuronal excitability and homeostasis; and gene expression. The DEGs we have identified likely provide at least some of the molecular substrates that underlie the numerous observations of sex differences in neuronal projections and synaptic plasticity and density (Cooke et al., 1998). In any event, given that individual sDEGs can measurably impact behavior, the large number of sDEGs we have uncovered may enable exquisitely specific regulation of sexually dimorphic social interactions.

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    Address correspondence and reprint requests to S. Marc Breedlove, Psychology Department, 3210 Tolman Hall, University of California, Berkeley, CA 94720-1650, Fax: 642-5293. Email:[email protected]

    ☆☆

    Paxinos, G

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