There is a link between sex hormones and the brain, and it is one not many people are aware of. Sex hormones can interact with certain parts of the brain, causing a variety of effects in both males and females. This article will uncover the link between sex hormones and the brain and the consequent effects of this relationship.
Sex hormones are a group of hormones that are responsible for sexual differentiation and reproduction. These hormones, also known as sex steroid hormones, are responsible for the different secondary sex characteristics observed in males and females as they approach puberty. Aside from the development of sexual characteristics, sex hormones also have other functions in the body. This includes regulating cholesterol, inflammatory response, and growth in certain body areas.
The site of production of sex hormones, in both males and females, is the gonads. For males, that is the testes; for females, the gonads are the ovaries. However, to a lesser extent, sex hormones can also be produced by various biochemical processes that convert certain steroids in the liver into sex hormones.
These sex hormones can be divided into two types: those prominent in males and those prominent in females, although both males and females have both types to a lesser extent.
The sex hormones in men are often known as androgens. While androgens are present in both men and women, androgens are the primary sex hormones in men.
The commonest of these androgen hormones is testosterone. This hormone is useful in bone and muscle development, hair growth (particularly facial hair), modulating sex drive, voice deepening, prostrate development, and the production of sperm. A testosterone deficiency can cause fatigue, low sex drive, and irritability, even in women.
Other types of androgens are androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and dihydrotestosterone.
The two primary female sex hormones are estrogen and progesterone. Estrogen is the major female sex hormone and is largely responsible for regulating puberty, menstruation, pregnancy, and menopause in women. As with testosterone, this hormone is also present in men but in much lesser amounts. The production sites of estrogen in the body include the ovaries (major), adrenal glands, and fat cells (minor).
Progesterone, the other major female sex hormone, is produced by the ovaries after ovulation. It regulates the menstrual cycle, supports pregnancy, and also leads to the suppression of estrogen production after ovulation. As with estrogen, progesterone levels decrease during menopause.
The role of sex hormones in the development of secondary sexual characteristics is well-documented. However, there are few comprehensive reports on the functions of these sex hormones in other systems and parts of the body. Nonetheless, research has identified a link between sex hormones and the brain. Observed locations of sex hormones in the brain include the following: neurons, presynaptic terminals, mitochondria, spine, apparatus, glial cells, and post-synaptic densities.
Studies have found that sex hormones can assist in the development of the brain and set circuitry that will be permanent. While these studies were carried out on animal models, the results offer some information about the relationship between sex hormones and the brain. For instance, estrogen results in permanent changes in the circuitry of the brain.
Therefore, the role of estrogen transcends puberty, pregnancy, menstruation, and menopause in women. Since estrogen is predominantly a female sex hormone, it raises questions about the relationship between sex hormones and the brain of the male species. However, studies show that neurons in the brain may manufacture estrogen out of testosterone in males. Furthermore, this production of estrogen from testosterone occurs around the time of birth and also permanently shapes brain circuitry. This is one of the sources of differences between the brains of males and females.
Additionally, researchers have found that the Y chromosome, which ultimately determines the sex of any baby, can trigger an androgen flood in the uterus in the first 12 weeks of pregnancy. This effect is through a gene known as SRY. The androgen flood, aside from determining brain circuitry in males, also helps in the development of the penis and testis.
Alterations in the levels of estrogen in the body can cause changes in mood, behavior, and energy balance. This is consistent with hormonal alterations in other parts of the body. For example, if the adrenal gland is not functioning optimally, symptoms like fatigue and anxiety may result.
One of the reasons for the adrenal gland not functioning well is stress. The body has an in-built stress-coping system known as the NeuroEndoMetabolic (NEM) Stress Response. The NEM system consists of six circuits that cut across several organs in the body. The hormone circuit is concerned with the various hormones in the body.
When there is chronic stress, the hormone circuit dysregulates. If this persists, a condition known as Adrenal Fatigue Syndrome (AFS) may result. Adrenal fatigue occurs when the body cannot keep up with life’s chronic stressors and is responsible for various symptoms.
Essentially, there is a delicate balance between the sex hormones in males and females. If this balance is upset, the hormones may have adverse effects on the brain. What’s more, these adverse effects may be long-lasting or even permanent.
It is no secret that the respective sex hormones in males and females direct the development of secondary sex characteristics. However, the relationship between these sex hormones and the brain in males and females may be different. As such, they can lead to sex differences in various parts of the brain.
Below, we examine this relationship and some of these sex differences, as found by multiple studies.
The hippocampus is an essential part of the limbic system, and it plays a significant role in learning and memory. The following are sex differences in the parts of the hippocampus due to stressors and varying sex hormones.
Chronic restraint stress lasting for three weeks causes apical dendrites of the CA3 hippocampal region to retract in males. Females do not exhibit this effect.
Male and female rats exhibit opposing effects of chronic stress on hippocampal-dependent memory, with males showing impairment and females showing augmentation or no impact.
Restraint and intermittent tail shock have different effects on classical eyeblink training in males and females, decreasing it in female mice and boosting it in the male species. In females, this effect is eliminated by removing the ovaries and is thus estrogen dependent.
Females are more sensitive to stress and have improved cognitive performance following stress. This explains why they get addicted in a short period. Ten days of chronic immobilization stress reduces the opioid system in men to the barest minimum. On the other hand, chronic stress for the same time period primes the opioid system in females. This then promotes excitation and learning processes.
Chronic restraint stress over three weeks promotes dendritic debranching and atrophy of neurons in the male rat’s medial prefrontal cortex. Females do not have dendritic alterations in these neurons, which project to cortical locations rather than the amygdala. Nevertheless, neurons that extend from the medial prefrontal cortex to the amygdala expand dendritically in females but not in males. This observation in females is estrogen-dependent, as indicated by females without ovaries not showing similar changes.
The results of the study were from observations of rat models. More studies are required to fully understand the relationship between sex hormones and the brain hippocampus.
The sex hormones in the brain cause sex differences in neurotransmitter systems, particularly the dopaminergic system. There is a sex variation in estrogen’s ability to increase dopamine release. Alongside dopamine, beta 1 adrenergic receptors in the striatum and likely in other areas of the brain are up-regulated after the removal of the ovary.
Estradiol (an estrogen steroid hormone) modulates dopamine release from the striatum in a sexually dimorphic manner. It does this through non-genomic estrogen receptors first discovered in the hippocampus and now found throughout the brain.
In cases of high stress and hormonal fluctuations, there may be alterations in the release of neurotransmitters. This is due to the dysregulation of the neuroaffect circuit, which includes the brain. As with the hormone circuit, if this dysregulation of the neuroaffect circuit persists, adrenal fatigue may result.
The cerebellum is the part of the brain that is primarily responsible for movement and balance. However, studies reveal that the cerebellum may have certain cognitive and mood functions. The cerebellum responds to estrogens, producing both estradiol and progesterone during development. It is associated with sex-specific conditions in humans.
In the growing cerebellum, estrogen controls the formation of dendrites and is important for the regulation of excitation and inhibition in the brain.
A growing body of research has focused on the neuroactive effects of ovarian steroids on cognition. The particular area of focus was how changes in estradiol and progesterone associated with the menstrual cycle might affect cognitive processes. While some studies found improved linguistics, an area where females typically excel, behavioral results appear to be inconsistent.
Researchers commonly record sex disparities in cognitive ability, for example, men surpassing women in spatial abilities. This substantial sexual dimorphism is likely a result of both biological and environmental variables, with biological analyses focusing on hormone impacts. Brain regions linked to cognitive functions, such as the hippocampus and prefrontal cortex, include androgen receptors, such as those for the sex steroid testosterone.
Sex hormones can exert sexual dimorphism on the body’s response to pain. This effect is via the androgen receptors in the gray matter of the midbrain. In relation to this, studies show that women are more sensitive to pain. This may explain why women have migraines more frequently than males and also why they record less success in getting rid of pain using morphine. Studies on responses to heat by male and female migraine patients also confirm a difference in the way migraine affects the brains of both sexes.
This refers to the mechanisms and strategies that protect the nervous system from injury and chronic degenerative disorders. Researchers have found that estradiol can shield neurons from potential damage by several neurodegenerative conditions, like Alzheimer’s and Parkinson’s. Note that the brain can produce estradiol from cholesterol or from androgens.
On their own, androgens also have some degree of neuroprotective abilities. The brain also appears to have the ability to manufacture androgen dihydrotestosterone from currently unknown precursors without ever needing the testis or ovaries.
It is well known that sex hormones are important for the development of secondary sex characteristics and reproduction in males and females. However, research shows that these hormones are also important in more ways than the reproductive system. There is a relationship between sex hormones and the brain.
These sex hormones result in different sex differences in different parts of the brain, like the hippocampus, prefrontal cortex, and cerebellum. Also, sex differences are observed in processes like pain sensitivity, cognition, empathy, and neuroprotection. While researchers have established these links in animal models, more work is required on humans for better understanding.
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Yes, the brain can locally manufacture estrogen to suit its estrogen needs. This is possible through various biochemical processes that convert testosterone to estrogen. Also, the brain can independently manufacture estrogen independent of the gonads. However, the precursors for this have not been identified.