Testosterone is an essential element in the story, but the story is massively complex in very surprising and interesting ways, making offhand comments about testosterone poisoning in males a poor indication of the facts. Before outlining the role of testosterone in aggression, it may be useful first to briefly address how human male and female brains differ and the mechanisms whereby these differences are established and maintained.
Normally, when a sperm fertilizes an egg, the resulting human conceptus has 23 pairs of chromosomes. A pair of sex chromosomes is either XX (genetic female) or XY (genetic male). In the early stages of development, the sex organs (gonads) of the fetus are neutral, but during the second month of fetal development, genes on the Y chromosome produce proteins that transform the neutral gonads into male testes. Absent this action, the gonads grow into ovaries. In the second half of development, testosterone produced by the fetal testes is released into the bloodstream and enters the growing brain. Testosterone now comes to affect the anatomy of the male brain.
How do sex hormones interact with the growing fetal brain? The fast answer is that a surge of testosterone masculinizes the fetal brain by altering the number of neurons in very specific areas that mainly concern reproductive behavior, such as mounting and penetrating. In the absence of the testosterone surge, the brain follows a typical female path. So the female brain plan can be thought of as the default—it is what you get unless testosterone masculinizes the brain. As we shall see, however, even when testosterone is available, other factors, including timing of testosterone release and the amount released, may mean that the brain is not masculinized after all or it may be masculinized to some lesser degree.
What does it mean to say that the brain is masculinized? Testosterone affects the number of neurons forming a network. More exactly, it prevents the death of neurons in the affected network. Consequently, several neuronal groups (nuclei) in the hypothalamus are more than twice as large in males as in females.
Why is there any cell death in a developing brain? In general, the developmental blueprint for making nervous systems allows for production of excess neurons. Then the neurons are culled as a function of how effectively the neurons are working in their networks. This is a bit like hiring extra players at the beginning of the football season and then culling them down to make the best team. Testosterone affects the developing brain by downregulating the culling process—the cell death. So the size of a region will reflect the amount of culling undergone. The pattern is laid down in the fetal brain but is maintained throughout life, with an additional testosterone surge in puberty. The circuitry that was organized by hormones in fetal development is activated by hormones during puberty.
Small but important correction: Once it passes from the blood into the brain, some testosterone is transformed by an enzyme into a more potent androgen, dihydrotestosterone. And some of that is then changed into estradiol, which goes on to masculinize the brain. Paradoxical though it may seem, estradiol, a female hormone, is crucial for the masculinizing development. Biology is funny that way. It uses whatever works to get the job done.
So why doesn’t the female fetal brain get masculinized? After all, the fetal ovaries make estrogen aplenty. Owing to genes on her XX chromosomes, the female fetus produces a protein that soaks up and destroys much of the circulating estrogen produced by the ovaries. This operation can vary, depending on the genes and timing of gene expression. Puzzling as it may seem, moreover, low levels of estrogen feminize the brain, whereas high levels masculinize it. Progesterone in the brain also helps to feminize the hypothalamus.