What Is the Main Idea?

Glutamate is the body’s main excitatory neurotransmitter, stimulating neurons to send signals around the body. In the free-access review article “Sex Hormones, Neurosteroids, and Glutamatergic Neurotransmission: A Review of the Literature”, published in the journal Neuroendocrinology, the authors summarize the current research evidence regarding whether or not there is a link between glutamate’s role as a neurotransmitter and the levels of sex hormones and neurosteroids in the body.

What Else Can You Learn

The role of the amino acid glutamate as a neurotransmitter in the brain is discussed. Sex hormones and neuropeptides, amino acids, and the general purpose of review articles are also discussed.

What Is Glutamate?

Glutamate is a naturally occurring amino acid that is found in the food we eat and is also produced by the body. It is a type of molecule called an “amino acid”. Amino acids are best known for being the component molecules that make up proteins, with the amino acids used and the order in which they are joined together in a protein influencing its functions, shape, and ability to interact with other molecules. If the order of the amino acids in a particular protein changes (for example if the gene that codes for it becomes mutated), the protein produced may no longer be able to function properly or even at all.

An example of this is when a single amino acid is changed in a protein called beta-globin because of a mutation in its coding gene. Beta-globin is a component of hemoglobin, which is found in red blood cells and is involved in carrying oxygen around the body. The single amino acid change creates a “sticky” patch on hemoglobin molecules that causes them to clump together and distort the red blood cells into a sickle shape, giving rise to a condition called sickle cell disease.

What Does Glutamate Do in the Body?

Glutamate plays several important roles in the body. It is a key component of metabolism, the process by which the food and drink that we consume is changed into energy, and can be broken down as an energy source in the brain when glucose levels are low. Glutamate is involved in the removal of excess nitrogen from our bodies via the production of urea (which is passed out of our bodies in urine). It is believed to be involved in the regulation of the sleep–wake cycle because levels are high during the rapid-eye-movement phase of sleep and when you are awake. Another major role of glutamate is as an “excitatory neurotransmitter”.

What Are Neurotransmitters?

Neurotransmitters carry chemical signals between neurons, a type of cell that transmits messages from one part of the brain and nervous system to another, and trigger an action or change in the target cell. This can be either “inhibitory” (it prevents or blocks the message from being transmitted any further), “modulatory” (it influences the effects of other neurotransmitters), or excitatory (it “excites” the target neuron, causing it to send the message on to the next cell).

Glutamate is the most abundant excitatory neurotransmitter in the human nervous system. It is involved in processes that take place in the brain such as memory and learning (it is estimated to be involved in more than 90% of the brain’s excitatory functions), and high levels of glutamate are also associated with increased pain levels. Glutamate is also converted into an important inhibitory neurotransmitter called gamma-aminobutyric acid (GABA) that is known as the “calming” neurotransmitter because it is involved in the regulation of anxiety, relaxation, and sleep. The process by which glutamate acts as a neurotransmitter is called “glutamatergic neurotransmission”.

What Are Sex Hormones and Neurosteroids?

Sex hormones are so called because they are critical in regulating the biological differences between males and females, and are particularly involved in reproduction and puberty (hormones are chemical messenger molecules that coordinate different processes and functions in the body). In humans, the key sex hormones are estrogen, progesterone, and testosterone. Neurosteroids are steroids that are produced in the brain or that have an effect on its functions (they can also act as signaling molecules). They are involved in a wide range of roles such as memory, learning, and behavior, as well as responses to stress and depression.

What Did This Article Look at?

Review articles are conducted as a sort of survey of all the information that has been published on a topic. Rather than presenting new findings, they aim to clarify current thinking on a topic and the evidence that supports it, and sometimes set out suggestions for changes to what is considered to be best practice. Increasing numbers of research articles are being published that are reporting a link between glutamate’s role as a neurotransmitter and the levels of sex hormones and neurosteroids in the body.

There is also evidence that changes to the regulation or levels of sex hormones and neurosteroids may be linked to the development of a range of neurological conditions. For example, dysregulation of glutamate’s role as a neurotransmitter has been linked to a number of disorders including epilepsy and post-traumatic stress disorder. It has also been linked to premenstrual dysphoric disorder, which is a severe form of premenstrual syndrome. It is therefore important that we gain a better understanding of how sex hormones and neurosteroids influence the normal functioning of the brain and identify any roles in the development of conditions that affect its function.

What Were the Review’s Findings?

The authors of the review concluded that the current evidence is that sex hormones can directly affect glutamate’s role as a neurotransmitter. In particular, there was evidence that estrogens can be protective against excitotoxicity, which occurs when excessive or prolonged activation of neurotransmission, particularly if mediated by glutamate, has a negative effect on neurons, leading to their loss of function or death. This is particularly relevant to stroke, where loss of blood flow (known as “ischemia”) in a region of the brain can not only damage neurons directly, but can also affect glutamate transport resulting in glutamate levels increasing to levels at which neurons die.

Other conditions known to be linked to too high levels of glutamate in the brain include Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, and chronic fatigue syndrome. Equally, levels of glutamate in the brain that are abnormally low are linked to low energy, trouble concentrating, and insomnia. Estrogen levels in the brain have also been shown to be linked to memory function in several non-human species. Progesterone may also have a neuroprotective effect although further research is needed to investigate the link.

There was some conflicting evidence regarding whether testosterone has a protective or negative effect on neurons, and a number of neurosteroids that are produced from the conversion of testosterone and progesterone may also play an independent role in altering the levels of glutamate in the brain. As we learn more about the relationships of sex hormones and neuropeptides with glutamate-mediated neurotransmission it is hoped that we will gain new insights regarding how to prevent the development of disorders and treat them more effectively.

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