“there is now increasing evidence that differences in brain function are prevalent across the sex divide, and that these differences manifest in surprising ways in animal models of both health and disease”
the preponderance of evidence supports the notion that humans undergo a hormonally mediated process of sexual differentiation of the brain just like animals.
Studies of laboratory animal models—for which social biases and constructs such as gender are absent—have revealed significant anatomical differences between the brains of males and females that arise in fetal and early postnatal development, as well as a role for hormones, which differ greatly between the sexes, in the functioning of the adult brain.
Many sex differences in adult brain structure and behaviors are the result of in utero organizational effects of gonadal steroid hormones, in particular androgens and their aromatized derivatives, estrogens, both of which are present in substantially higher concentrations in male fetuses due to testicular steroidogenesis.
A mammalian embryo is female by default. Males develop when the Sry gene of the Y chromosome is expressed, spurring the development of testes. During fetal development, the testes produce large amounts of testosterone, much of which is converted to estrogen. Both hormones then act on the brain, inducing the cellular process of masculinization…By default, the gonadal precursor will differentiate into an ovary; formation of a testis requires a transcription factor coded for by the Sry gene on the Y chromosome. Likewise, the brain will develop as a female brain by default and be directed towards masculinization only if exposed to the steroids produced by the testis.
Developmental masculinization of the brain leads to significant structural differences in the brains of the two sexes:
- Some brain regions are larger in males; others are smaller.
- Collections of cells that constitute nuclei or subnuclei of the brain differ in overall size due to differences in cell number and/or density, as well as in the number of neurons expressing a particular neurotransmitter.
- The length and branching patterns of dendrites and the frequency of synapses also vary between males and females—in specific ways in specific regions—as does the number of axons that form projections between nuclei and across the cerebral hemispheres.
- Even nonneuronal cells are masculinized. Astrocytes in parts of the male brain are more “bushy,” with longer and more frequent processes than those in the same regions of the female brain. And microglia, modified macrophages that serve as the brain’s innate immune system, are more activated in parts of the male brain and contribute to the changes seen in the neurons.
Another region of the brain that is masculinized during development is the amygdala, which in addition to its roles in the processing of emotions is a key region regulating social play behavior by juveniles, sometimes called rough-and-tumble play, which differs markedly in males and females across a wide range of species. The dimorphism in the frequency and intensity of play is particularly interesting in that it is expressed during a time of life when there are minimal to no circulating steroids, and thus any differences in males and females are either genetic or the result of earlier organizational effects of steroids on the brain.
DNA methylation is critical to the maintenance of feminization by actively repressing masculinization genes.
However, while both the popular and scientific presses make reference to “male” and “female” brains, the brain is in reality not a unitary organ like the liver or the kidney. It is a compilation of multiple independent yet interacting groups of cells that are subject to both external and internal factors. This is abundantly true for hormonal modulation, with many and varied signal transduction pathways invoked. As a result, it is quite literally impossible for the brain to take on a uniform “maleness” or “femaleness.” Instead, the brain is a mix of relative degrees of masculinization in some areas and feminization in others. On average, there are likely to be some areas that are more strongly feminized in a female and others that are more strongly masculinized in a male, but averages are never predictive of an individual’s profile. Moreover, a mosaic is not a blend—there is not a continuum of maleness to femaleness—and there are many parameters that are neutral in regard to sex, with no consistent differences between males and females.