Many of us think of hormones as the gender-specific molecules we learned about in middle school health class—little chemical messengers that govern our reproductive development and behaviors. But sex steroids like testosterone and estrogen have reach beyond our nether regions and reproductive behaviors. They affect the entire brain both during development and throughout adult life: shaping, activating, and fueling sexually dimorphic brain circuits involved in stress and memory as well as several psychiatric disorders.
Sexual dimorphic brain development
Sex is determined by two chromosomes: men have one X chromosome and one Y chromosome, while women have two X chromosomes. The Y chromosome contains the SRY gene, which triggers a flood of androgens (the group of hormones that includes testosterone) sometime between six and twelve weeks of gestation, guiding the development of the penis and testes. But this fetal testosterone bath also makes its mark on the brain’s architecture, resulting in sexually dimorphic brain circuits.
Sexual dimorphism is an observable, phenotypic difference between the males and females of a given species. Think of peacocks and sexually dimorphic tails: males have the long, brightly colored feathers while females have shorter, duller plumage. But sexual dimorphism is not just limited to our outsides. The human brain also shows visible differences in various brain regions between men and women. Predictably, these differences can be seen in areas like the hypothalamus, implicated in sexual and reproductive behaviors. But researchers have also noted differences in circuits linked to memory, emotion, and stress. Women show slightly larger volume in regions like the frontal and limbic cortexes while men have more bulk in the amygdala and parietal lobe.[i]
Sex differences are also observable at the cellular level.[ii] Men and women show differences in both cell and receptor density in certain areas. For example, women show greater density of neurons in particular language areas as well as in the frontal lobe. It is also interesting to note that most of these sexually dimorphic regions are those that have the highest density of sex steroid receptors. This allows these circuits to be laid down during prenatal and early childhood development and then activated at puberty, when hormones flood the body again.
While the study of sexual dimorphism is controversial—author Cordelia Fine coined the provocative if not entirely accurate term, “neurosexism,” in her book Delusions of Gender[iii]—far too often findings in this field are unnecessarily sensationalized by the media. It is important to note that differences in the brain do not necessarily denote better cognition or function as some suggest. In fact, Geert de Vries, a researcher at the University of Massachusetts Amherst, has suggested that some of these sexually dimorphic brain circuits may actually be compensatory, different enough so that men and women, who have different levels of sex steroids coursing through the bloodstream and the brain, can have similar behavioral output.[iv] Thus, in some activities, such as solving spatial problems or using short-term memory, these brain differences allow men and women to use different strategies to perform at the same level.
Hormones can act as neurotransmitters
Hormones are essential to cell metabolism and homeostasis. You will find cell receptors for sex steroids across the body—they receive hormone messengers released into the bloodstream by endocrine glands like the pituitary gland and the thyroid gland.
The brain also has a wide distribution of hormone receptors, allowing sex steroids to affect circuits across the entire brain—not just the hypothalamus and areas of the brain linked to sexual behavior. Like neurotransmitters, sex steroids like estrogen and testosterone can influence communication between brain cells. In fact, scientists have identified several different types of testosterone and estrogen receptors that alter neural signaling in different ways, like changing the properties of the cell membrane or influencing the release of other neurochemicals from the cell.[v] And they admit that there may be receptor types, and methods of action, that have yet to be identified.
Hormones may act as mediators, helping other neurotransmitters or neuropeptides change signal propagation in the synapse, or work directly on the cell themselves. Researchers who study hormones at the cellular level often refer to them as “gate openers,” helping cells to mediate the neural signal, which may ultimately influence human behavior by directing attention or making environmental stimuli more salient.[vi]
Hormones, cognition, and psychiatric disorders
Most psychiatric disorders show different prevalence rates between the sexes. Depression is more commonly seen in women, while schizophrenia afflicts more men. Current research studies suggest some of those differences may be linked to hormones and how they act upon sexually dimorphic brain circuits. For example, researchers recently demonstrated that women with major depressive disorder had hypoactivation (or low activation) in the brain’s stress circuitry, linked to low estradiol (a form of estrogen) and high progesterone.[vii] Other work has shown differences in working memory, emotional memory, and the stress response during different parts of the menstrual cycle.[viii] Similarly, low testosterone levels have been linked to increased vulnerability for psychosis in males.[ix]
Neuroscientists have only scratched the surface in understanding all the ways that hormones influence cognition and behavior—mostly because research programs have historically often studied only the males of the species. But there is a paradigm shift occurring in the field, inspiring scientists to take a closer look at hormones and sex in their research, which should afford us greater understanding of the many different ways sex steroids impact the brain.
[i] Goldstein JM, Seidman LJ, Horton NJ, Makris N, Kennedy DN, Caviness Jr VS, Faraone SV and Tsuang MT. Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging. Cerebral Cortex, 2001, 11(6): 490-497.
[ii] Cahill L. His Brain, Her Brain. Scientific American, May 2005: 40-47.
[iii] Fine C. Delusions of Gender: How Our Minds, Society, and Neurosexism Create Difference. 2011. W.W. Norton & Company, New York.
[iv] McCarthy MM and Arnold AP. Reframing sexual differentiation of the brain. Nature Neuroscience, 2011, 14(6): 677-683.
[v] Chaban V, Li J, McDonald JS, Rapkin A and Micevych P. Estradiol attenuates the adenosine triphosphate-induced increase of intracellular calcium through group II metabotropic glutamate receptors in rat dorsal root ganglion neurons. Journal of Neuroscience Research, 2011, 89(11): 1707-1710.
[vi] Micevych P and Dominguez R. Membrane estradiol signaling in the brain. Frontiers in Neuroendocrinology. 2009, 30(3): 315–327.
[vii] Holsen LM, Spaeth SB, Lee JH, Ogden LA, Klibanski A, Whitfield-Gabrieli S and Goldstein JM. Stress response circuitry hypoactivation related to hormonal dysfunction in women with major depression. Journal of Affective Disorders, 2011, 131(1-3): 379-387.
[viii] Goldstein JM, Jerram M, Abbs B, Whitfield-Gabrieli S and Makris N. Sex differences in sex response circuitry activation dependent on female hormonal cycle. Journal of Neuroscience, 2010, 30(2): 431-8.
[ix]Van Rijn S, Aleman A, de Sonneville L, Sprong M, Ziermans T, Schothorst P, van Engeland H and Swaab H. Neuroendocrine markers of high risk for psychosis: salivary testosterone in adolescent boys with prodromal symptoms. Psychological Medicine, 2011, 41(9): 1815-22.