Steroid hormones like testosterone and estradiol are able to pass through the phospholipid membrane of a neuron. Some neurons express receptors for these hormones. Androgen receptors bind androgens like testosterone while estrogen receptors bind estrogens like estradiol. When a hormone binds to a receptor in the neuron, the hormone-receptor complex dimerizes and moves into the nucleus where it can bind to specific sites on the DNA and act as a transcription factor to turn on or off certain genes.

Animation 361. Steroid hormones, like testosterone and estradiol, can cross the cell membrane without assistance. In the cell, the hormones can bind to hormone receptors, which dimerize, move to the nucleus, and act as transcription factors on the DNA. ‘Testosterone Action’ by Casey Henley is licensed under a Creative Commons Attribution Non-Commercial Share-Alike (CC BY-NC-SA) 4.0 International License.

Testosterone Pathways in the Cell

When the testes secrete testosterone during the prenatal critical period, the effect is to masculinize and defeminize the brain, body, and behavior, and this is accomplished through the transcription of a specific set of genes. However, many of those genes are not transcribed by the action of androgen receptors interacting with the DNA. When testosterone enters the cell, it does not always bind to androgen receptors. Some neurons also express proteins that can break testosterone down into its metabolites. 5-alpha reductase converts testosterone into dihydrotestosterone, or DHT, another androgen that is able to bind the androgen receptor. The enzyme aromatase converts testosterone into estradiol, an estrogen that can bind to the estrogen receptor.

Estrogen Effects

In some mammals, like rodents, this conversion of testosterone to estradiol is the main process by which neurons and the brain are masculinized. The estrogen receptors cause the transcription of masculinizing genes. Therefore, somewhat surprisingly, even though estrogen is typically thought of as a female hormone, its actions during development are responsible for much of the masculinization that occurs in the brain in some animals. It should be noted, though, that estrogen does not appear to have these same masculinizing effects during human development.

Animation 36.2. After testosterone enters the cell, if it does not bind to an androgen receptor, it can be metabolized by enzymes in the cell. 5-alpha reductase converts testosterone into dihydrotestosterone. DHT, like testosterone, can bind to an activate androgen receptors. The enzyme aromatase converts testosterone into estradiol. Estradiol is an estrogen and can bind to and activate estrogen receptors. During developmental critical periods, the aromatization of testosterone to estradiol leads to the transcription of masculinizing genes in some animals like rodents. ‘Aromatization’ by Casey Henley is licensed under a Creative Commons Attribution Non-Commercial Share-Alike (CC BY-NC-SA) 4.0 International License.

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