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The Paraventricular Nucleus: Hidden Culprit in Adrenal Fatigue?

A concept image of the paraventricular nucleus playing a roll in adrenal fatigueWe tend to see adrenal fatigue as a condition arising from the adrenal glands. However, there is some evidence that it might actually start in the brain. To be more precise, in the paraventricular nucleus of the hypothalamus.

The hypothalamus, as part of the hypothalamic-pituitary-adrenal (HPA) axis, is the initiator of the cascade of events throughout your body when stress is perceived - your NeuroEndoMetabolic (NEM) stress response - resulting in the release of adrenaline and cortisol. In turn, this affects all body systems, resulting in an increased heart rate and breathing, readiness to run or fight or freeze, and a decrease in certain bodily functions deemed not necessary for immediate life.

Your adrenal glands do the most work during this time, producing inordinate amounts of cortisol as demanded by the brain. However, long-term elevated cortisol production can have a negative impact on your health, depleting the body and eventually leading to adrenal fatigue. As you move through the stages of adrenal fatigue, your body presents a number of symptoms that may seem totally unrelated, making this condition very difficult to detect.

Thus, finding ways to identify and manage adrenal fatigue is paramount to healing from the serious symptoms it causes. However, due to its role in the hypothalamus, there is a possibility that the paraventricular nucleus plays a major role in the imbalances that lead to adrenal fatigue, and could point to a path for healing.

But what is the paraventricular nucleus, what does it do, and what is its role in adrenal fatigue?

The Paraventricular Nucleus

The paraventricular nucleus is situated in the hypothalamus. It is a group of neurons, more specifically, magnocellular, parvocellular, and long-projecting neurons. These play an essential role in regulating various endocrine activities and with energy balance. When the paraventricular nucleus is compromised, or no longer functioning as it should, a number of symptoms are usually the result. These include, for example, a decline in cognitive function, migraines, reactive hypoglycemia, blurred vision, sleep issues, and fatigue.

A compromised paraventricular nucleus also implies that the allosteric control of leptin is lost. Allosteric control refers to the inhibition or activation of an enzyme at a site different than the active site where an activity occurs. As a result, the enzyme’s original function may be inhibited when the paraventricular nucleus is compromised.

The Role of Leptin

A concept image of the paraventricular nucleus and leptin reactionLeptin, which is often referred to as the “fat hormone,” is also the “starvation hormone.” It is made in your body’s fat cells. From there, it moves to the brain via your blood and informs your brain that there is sufficient fuel for energy, that it can take part in exercise, and that your body is ready for pregnancy, for example.

When your leptin levels are too low, your brain registers that you are starving. This stimulates your hunger, and you may start eating more than what is normal, possibly gaining weight in the process. Essentially, when your body goes into a state of starvation (whether real or perceived), it tries to conserve as much energy as possible – in the form of fat.

This process takes place in the paraventricular nucleus of your hypothalamus. The hormone leptin activates the parvocellular oxytocin neurons of your hypothalamic nucleus, which then increase your body’s energy expenditure and contributes to weight reduction.

Studies have shown, however, that in cases of long-term fasting or severe calorie restriction, your leptin levels may be so low that the paraventricular nucleus indicates a state of starvation. One could be obese but have lower leptin levels, with the brain indicating a state of starvation and the appetite increasingly stimulated to eat more. Essentially, your brain does not get the message that you need to stop eating, and you develop what is referred to as ‘leptin intolerance’. In other words, your brain says you are starving while your body gains pounds.

Because of leptin’s ability to modulate appetite by its action on the paraventricular nucleus, many people have come to see leptin supplementation as a means of losing weight. The problem for overweight people, however, is that their bodies produce enough leptin – their brains are just not registering this. Leptin supplementation could, instead, result in even more weight gain.

Interestingly, studies show that exercise plays no role in modulating leptin production in any way. Leptin is your body’s indicator of the amount of energy it has available and is one of the signals of your brain’s parasympathetic system activity. Obesity, at its core, is the result of inflammation in the brain and a compromised signaling system. When your body’s energy balance is out of sync, your leptin signaling is compromised.

Compromised leptin is indicative of a wider hormone issue. When your hormones are in a state of imbalance, your brain’s signaling goes haywire, as do many of your body’s physiological functions, with myriad symptoms manifesting. One of these is adrenal fatigue and its own subset of related symptoms.

Symptoms commonly associated with adrenal fatigue include, amongst many others, fatigue, anxiety, depression, brain fog, blood sugar issues, hormone imbalance, and skin issues.

The Hypothalamus’ Role

An image of the paraventricular nucleus within the hypothalamusThe hypothalamus is located near the pituitary gland at the base of your brain. It plays a role in many functions, such as appetite control, libido, hormone release, emotions, and body temperature. One of the most important functions of the hypothalamus is that it links three major systems: the immune system, endocrine system, and central nervous system. The exact point where these three systems meet is the paraventricular nucleus.

The hypothalamus consists of three areas:

The anterior region (supraoptic region)
The major nuclei found here are the supraoptic and paraventricular nucleus. The main function in this portion of the hypothalamus is related to hormone release, with many of these hormones directly interacting with your pituitary gland.

Amongst these hormones are included:

  • Corticotropin-releasing hormone (CRH) which is involved with your stress response. It signals your pituitary to gland to produce neurotransmitters that trigger cortisol production in the adrenal glands.
  • Gonadotropin-releasing hormone (TRH) which stimulates your pituitary gland to produce reproductive hormones.
  • Vasopressin, a hormone that helps regulate your body’s water levels.
  • Thyrotropin-releasing hormone (TRH) which stimulates the pituitary gland to produce thyroid stimulating hormone. The latter plays a role in heart, muscle, and gastrointestinal function.
  • Oxytocin, a hormone that plays a role in emotions and behavior, such as trust and recognition. It is also involved in certain reproduction functions.
  • Somatostatin which encourages the pituitary to release certain hormones such as those mentioned above, as well as growth hormones.

Besides its function with regards to hormone release, the anterior region is also involved in body temperature regulation and the circadian rhythm.

The middle region (tuberal region)
The nuclei found in this region are mainly involved in releasing hormones that stimulate the pituitary gland to produce growth hormone. Growth hormone is responsible for your body’s growth and development.

The posterior region (mammillary region)
This area plays a role in body temperature regulation and sweat production. It may also play a role with regards to memory, although this is still unclear.

Adrenal Fatigue, Neurotransmitter Imbalance, and Inflammation

It is the HPA axis that starts a cascading effect throughout the body the minute stress is experienced. It does not matter the source of the stress, whether psychological, physical, or environmental in nature, the end result is a series of changes that affect all aspects of your physiological function. This automatic response is known as the NeuroEndoMetabolic (NEM) Stress Response.

Your HPA axis, which includes the paraventricular nucleus, triggers more than fifty hormones that help you deal with stress. The HPA axis, however, together with your adrenal glands, are put into overdrive if your body is exposed to long-term or chronic stress.

Although stress is usually of short duration (thus not causing any damage to your body), long-term stress can lead to numerous important functions either slowing down or shutting down entirely. In the long-run, this can have serious consequences to your health, as the symptoms presented may vary so greatly that accurately identifying the root cause of the condition may be extremely difficult.

As you progress through the various stages of adrenal fatigue, you may find that your symptoms worsen, with new ones possibly forming. The latter stages of the condition could leave you bedridden or even result in death.

Adrenal fatigue is the end-result of severe stress. The earlier stages of the condition may see a rise in the anti-stress hormone cortisol, but the advanced stages see your adrenal glands tiring, and a decrease in cortisol production. Once the adrenals are exhausted, your body encounters a state of cortisol deficiency.

HPA axis regulation is closely associated with neurotransmitter regulation. Both need to function correctly in order for balance. If one becomes unbalanced, so does the other. The problem may arise with an increased cortisol production that results in fewer precursor hormones being available for the production of other hormones in the body. This may directly affect, or be affected by, the chemical messages received by or transmitted from the paraventricular nucleus.

Neurotransmitter Function

Many sticky notes to indicate an issue with the paraventricular nucleus and neurotransmittersThe neurotransmitters, or chemical messengers, in the brain are the messengers that transmit signals between your neurons. This allows for communication between different areas in the brain as well as between the brain and your different body systems. These neurotransmitters regulate every function in your body, including your mental state, sleep patterns, pain perception and response, and cognitive health.

A ‘malfunction’ in the paraventricular nucleus may result in faulty neurotransmissions that, in turn, may result in health conditions, such as a hormone imbalance. Your nerve cells communicate with one another via tiny circuits called neuronal pathways. Our nerve cells do not touch each other; there is a small space between each two nerve cells called a synaptic cleft. Neurotransmitters are responsible for transmitting messages from one nerve cell via a synaptic cleft to another. As soon as a message is transmitted, the space between these two nerve cells is filled with serotonin. This process is repeated over and over until the message or ‘signal’ reaches its intended target and an action is initiated.

Your body’s main neurotransmitters are dopamine (precursor to norepinephrine and adrenaline), norepinephrine (for the sympathetic nervous system), adrenaline (for the sympathomedullary nervous system), acetylcholine (for the parasympathetic nervous system), and serotonin, the feel-good hormone.

These neurotransmitters act much faster than cortisol, the stress hormone. An imbalance in these hormones may cause numerous unrelated symptoms, such as anxiety, hyperactivity, cravings, paranoia, brain fog, compulsive behavior, inflammation, panic attacks, blood pressure issues, symptoms of hyperthyroidism, secondary hypothyroidism, impaired cognitive function, immunological imbalance, gastrointestinal and cardiovascular problems, depression, and issues with your circadian rhythm such as insomnia, amongst many others.

The following conditions may often be associated with the more advanced stages of Adrenal Fatigue Syndrome (AFS):

  • Irritable bowel syndrome (IBS) or leaky gut
  • Tourette’s Syndrome
  • Fibromyalgia
  • Obsessive-compulsive disorder (OCD)
  • Parkinson’s disease
  • Forgetfulness
  • ADD or ADHD
  • Chronic pain
  • Obesity
  • Anxiety, panic attacks, and depression
  • Conditions related to eating disorders such as anorexia nervosa and bulimia
  • Bipolar disorders

The Inflammatory Response

There is a strong correlation between adrenal fatigue and inflammation, with inflammation playing an integral role in many of the symptoms associated with the condition. Amongst these are anxiety, depression, blood sugar issues, and various aches and pains.

Of itself, inflammation plays a prominent role in the body’s ability to repair itself, as it allows you to fight against and get rid of dangerous pathogens and invaders that cause you harm. Unfortunately, the symptoms associated with inflammation, such as pain, heat, swelling, and redness, tend to be side effects.

Please keep in mind when going through this section that a dysregulation in certain neurotransmitters in the paraventricular nucleus may be associated with inflammation, as has been mentioned.

A body inflamed due to a malfunctioning paraventricular nucleusWhile inflammation is a natural, biological response to stress, long-term psychological stress and chronic infection could lead to an inflammation circuit that is constantly activated. This results in a state of imbalance that leaves your body more susceptible to contracting a wide variety of health conditions, many of which are associated with the aging process. The impact of this type of inflammation may take years before you actually experience it and may, in many instances, be the cause of numerous chronic conditions.

Typical signs of chronic inflammation include IBS, dizziness, depression, brain fog, sensitivities to certain foods, and anxiety. While inflammation may be a response to stress, inflammation could also be a contributing factor that increases stress. Inflammation may thus have a negative effect not only on your physical wellbeing but your mental wellbeing as well.

Conditions that have an inflammation aspect associated with them include, amongst others:

  • Autism
  • Asthma
  • Fibromyalgia
  • Lupus
  • Cancer
  • Acid reflux
  • Arthritis
  • Diabetes
  • Osteoporosis
  • Heart conditions
  • Skin conditions like psoriasis or acne
  • High blood pressure

One of the causes of inflammation is dysbiosis of the gut, when the gut has an imbalance of “good” and “bad” bacteria. This dysbiosis results in the immune system acting to protect the body, resulting in infection. Do take note that, as mentioned above, certain hormones released by the paraventricular nucleus play a role in metabolism.

Addressing the Issue

Elevated Cortisol Levels

When it comes to adrenal fatigue and a compromised paraventricular nucleus, there is no quick fix. Too many body systems and procedures are involved, all of which, in some way or the other, have been compromised. It must be remembered that the first stages of adrenal fatigue see a marked rise in cortisol levels, while the later stages see a marked decline.

When it comes to controlling elevated cortisol levels, the first step is often to control your eicosanoid hormone system. Eicosanoids, although very similar to hormones, tend to act locally, and are usually made very close to the area of the body in which they are needed. They play a role in blood pressure regulation, blood clotting, fever, and inflammation. They also have an influence on your body’s immune response as well as some respiratory and reproductive processes. These eicosanoids play an important role in the release of leptin, which has an active role in the function of your paraventricular nucleus.

Decreased leptin production may be synonymous with elevated cortisol levels. A leptin supplement may thus be considered when cortisol levels are higher than normal. You could also consider other health supplements or foods that contain curcumin. Green tea and certain herbs are also good options.

Please, however, do not summarily start using leptin or other supplements without first consulting a qualified health care professional who is well-versed in adrenal fatigue, or a compromised paraventricular nucleus. The wrong supplements, or incorrect doses, could cause havoc on an already weakened body.

Checking on alterations in your leptin levels is seldom done by those in the medical profession, although it is a relatively good indicator as to whether your hormone levels are balanced or not.

High cortisol levels could play havoc on your chemical messengers, depleting them as time goes by. Unfortunately, your brain is unable to function correctly without its store of neurotransmitters, nor is it able to adequately send signals to other parts of your body.

Suppressed Cortisol Levels

An image depicting suppressed cortisol levels and the paraventricular nucleusSuppressed cortisol levels are usually indicative of the latter stages of adrenal fatigue. Your adrenals struggle to keep up with the cortisol demanded by your body and wear out. As a result, your precursor hormones are used to make cortisol in order to meet the demand. The production of certain vitamins, such as vitamin D, which is made by the body, for example, are down-regulated. This results in a higher cortisol ratio as compared to other hormones, resulting in a situation that inhibits your paraventricular nucleus function.

In order to address this situation, one needs to restore the hormonal balance in the brain, especially in the paraventricular nucleus area of the hippocampus. This could conceivably be accomplished by the addition of progesterone and other depleted hormones. The preferable scenario, however, is to not let things get this out of hand in the first place. Getting enough sunlight is also a good idea, as it is needed for vitamin D development, while oxytocin helps exercise new neural networks. One of the ways oxytocin is released in the body is by means of an orgasm and can help you to reset your circadian rhythm while producing massive amounts of antioxidants that are needed to repair the circuits present between the hypothalamus, paraventricular nucleus, and pituitary gland.

The brain makes just about all the chemicals it needs to function correctly, while the paraventricular nucleus influences both the sympathetic and parasympathetic nervous systems. By focusing attention on the paraventricular nucleus and its general function, one could quite conceivably prevent the incidence of adrenal fatigue. If you already have adrenal fatigue, however, you may need to focus your healing on this part of the brain in order to address the issue on a physiological scale.

In Closing

Inflammation could cause a disruption in the signaling ability of the paraventricular nucleus. When its signaling ability is compromised, it results in a system-wide imbalance encompassing just about every aspect of your bodily function. Adrenal fatigue and its myriad associated conditions are but symptoms of this event.

A young man thinking clearly with his paraventricular nucleusAs the brain is the most important muscle in the body, it does everything it can to preserve itself. In so doing, it may take energy from other systems and organs, at the same time causing problems from hormone imbalances, to inflammatory health conditions, to heart conditions, and more.

It is the brain that first perceives a threat – any kind of threat – whether psychological, physical, or environmental in nature, and it is the brain that starts the cascading reaction that allows us to deal with it. This reaction includes the downregulation of certain bodily functions. Whereas everything returns to normal once the threat has passed, in instances where the brain incorrectly perceives this threat as persistent, adrenal fatigue and its complications are the result. And the paraventricular nucleus stands right in the middle of the situation. Thus, the health of the paraventricular nucleus should be seen as paramount in the effort to combat adrenal fatigue and its myriad consequences.

© Copyright 2019 Michael Lam, M.D. All Rights Reserved.

Dr. Lam’s Key Question

Actually, yes, a dysfunction of the paraventricular nucleus most certainly can contribute to obesity. The paraventricular nucleus is dependent on hormones that act as neurotransmitters to function correctly. When something happens to cause a hormonal imbalance, obesity may be one of the resulting conditions.

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