serotonin resistance- it's real

[DAVID]

Many physicians said that low serotonin is the culprit with aging and insomnia. For sure aging people have low sex hormone and serotonin resistance

My hypothesis is that aging people have more serotonin in the blood but have problem with serotonin resistance... High carbs diet, low sex hormone and stress disturb serotonin pathway


The whole country – meaning Baby Boomers – are being prescribed AmbienSR®, Lunesta®, Sonata®, Prozac®, Zoloft®, Paxil®, Seraquel®, , Sarafem®, Effexor®, Celexa®, Cipramil®, Seroxat®, Aropax®, Lexapro®, Cipralex®, Luvox®, Faverin®, Cymbalta®, Wellbutrin®, Zyban®, Elavil® and Ativan®, Xanax® and Valium®. All of these drugs have soporific side-effects and some of them are just garden variety sleeping pills.

Mid-life means broken sleep and broken sleep means high serotonin levels that never had the chance to convert to melatonin in the dark and drop while you slept, because you didn’t.

Serotonin that can’t convert in normal daily rhythms up and down will enact a fear response – like paranoia, panic or that feeling of trying to wade through peanut butter. In nature, serotonin goes up in response to “fight or flight” scenarios because serotonin is needed to metabolize stress hormones like cortisol.The drugs mentioned above are predominantly SSRIs, some with a little nor-epinephrine effector added as a “chaser”. SSRIs are medications that evolve their effects at the serotonin transporter. They increase the level of serotonin by inhibiting its reuptake into the presynaptic void.Why would we need drugs to increase our serotonin, when we never sleep and it can’t drop? Because the range serotonin is in matters more than if it’s high or low. Low serotonin means no impulse control, high serotonin means numb or no effect.

The more carbohydrate you eat the higher your serotonin goes. Self-medicating with cake or pasta is just as effective as Paxil.

[hardasnails1973]

Endocrine system works as a symphony when one section of the orchestra is not playing the whole concerto is messed up. Thyroid and adrenals imbalances affect serotonin levels. old people tend to have excess of cortisol which will deplete serotonin on other hand people can have low cortisol and can not ruse thyroid effectively which will alter sertonin metabolism. Testosterone fits in here as wel. I still have not found that low testosterone affects serotonin metabolism yet, but It must do something since it causes depression (grumpy old man syndrome) People that are paxil resistant instead of increasing their meds drs should look towards thyroid and adrenal imbalances first, but which ones do that

[Naturdoc]

Serotonin resistance, if it exists, would most easily be treated by raising serotonin levels as in insulin or thyroid resistance. SSRIs raise serotonin levels in the synapse, not body levels. Serotonin levels can be measured through neurotransmitter testing.

[marianco]

Originally Posted by DAVID

Many physicians said that low serotonin is the culprit with aging and insomnia. For sure aging people have low sex hormone and serotonin resistance

My hypothesis is that aging people have more serotonin in the blood but have problem with serotonin resistance... High carbs diet, low sex hormone and stress disturb serotonin pathway


The whole country – meaning Baby Boomers – are being prescribed AmbienSR®, Lunesta®, Sonata®, Prozac®, Zoloft®, Paxil®, Seraquel®, , Sarafem®, Effexor®, Celexa®, Cipramil®, Seroxat®, Aropax®, Lexapro®, Cipralex®, Luvox®, Faverin®, Cymbalta®, Wellbutrin®, Zyban®, Elavil® and Ativan®, Xanax® and Valium®. All of these drugs have soporific side-effects and some of them are just garden variety sleeping pills.

Mid-life means broken sleep and broken sleep means high serotonin levels that never had the chance to convert to melatonin in the dark and drop while you slept, because you didn’t.

Serotonin that can’t convert in normal daily rhythms up and down will enact a fear response – like paranoia, panic or that feeling of trying to wade through peanut butter. In nature, serotonin goes up in response to “fight or flight” scenarios because serotonin is needed to metabolize stress hormones like cortisol.The drugs mentioned above are predominantly SSRIs, some with a little nor-epinephrine effector added as a “chaser”. SSRIs are medications that evolve their effects at the serotonin transporter. They increase the level of serotonin by inhibiting its reuptake into the presynaptic void.Why would we need drugs to increase our serotonin, when we never sleep and it can’t drop? Because the range serotonin is in matters more than if it’s high or low. Low serotonin means no impulse control, high serotonin means numb or no effect.

The more carbohydrate you eat the higher your serotonin goes. Self-medicating with cake or pasta is just as effective as Paxil.

1. I would dispute the assertion that low serotonin is the primary cause of age-related insomnia.

Serotonin, other neurotransmitters, hormones, and immune-system cytokines are highly linked in their production. The nervous system, endocrine system, and immune system form one system, which I call the mind, which is organized like a computer chip circuit - where in place of electrons traveling through wires, chemical messengers travel through a fluid to transport information. There are thousands if not millions of these chemical messengers, which can work in combinations.

This makes the mind much more extremely complex than the best computers (which only use one messenger - the electron, which can transmit only one message (either on or off). There are 1.1 trillion cells in the brain which is the most important organ of the nervous, endocrine, and immune systems. This combined with the billions of other nervous, endocrine, immune system cells makes for an extremely complex information processing system.

The neurons which release serotonin, the neurons which release dopamine, and the neurons which release norepinephrine, etc. exist as separate groups of neurons, which regulate large groups of other neurons. These regulatory neurons are organized as circuits, which can in turn control one another. For example, there are circuits of dopamine-releasing and serotonin-releasing neurons which reduce the release of norepinephrine from the norepinephrine-releasing neurons. Some acetylcholine-releasing neuron circuits can control dopamine-releasing neurons. Etc.

When serotonin is low, there may be other problems contributing to it which may be the more direct factor in causing insomnia.

For example, when thyroid hormone is low (which occurs in up to 40-50 percent of people depending on the country), serotonin production is lowered because thyroid hormone acting on presynaptic serotonin receptors, determines serotonin production. Hypothyroidism can cause insomnia.

When adrenal fatigue is present, norepinephrine production and release is increased to force more output from the adrenal glands. To increase norepinephrine, the brain reduces serotonin production. It is the high norepinephrine levels which keeps the person awake. Further, in adrenal fatigue, the lower production of cortisol prevents cortisol from reducing Corticotropin Releasing Hormone production. Reducing CRH causes a reduction in norepinephrine production.

2. Self-medication with carbohydrates is not the same as taking Paxil.

Paxil is a complex medication which has multiple mechanisms of action. For example, it increases serotonin levels by blocking reuptake. It can block acetylcholine receptors. It can block histamine receptors - which can cause sedation. It can block norepinephrine receptors. It can increase norepinephrine level by blocking reuptake. it can increase dopamine level by blocking reuptake or by increasing serotonin levels near some dopamine neurons, which have a dopamine reuptake transporter which can be blocked by serotonin, etc. It can block Cytochrome P450 2D6. etc.

Why do some people self-medicate with carbohydrates. The answer is that it serves a purpose. What is that purpose? The answer is that the person has difficulty in producing their own carbohydrates (i.e. glucose) from fat or protein because of impaired gluconeogenesis, which can occur with cortisol deficiency, i.e. adrenal fatigue or insufficiency. The presence of cortisol deficiency results in a rise in norepinephrine production and release, which then keeps the person awake.

3. Melatonin deficiency can occur as one ages - as a consequence of the aging brain and difficulty in producing melatonin - not serotonin.

Melatonin is made from serotonin. But the production of serotonin in serotonin-releasing neurons is independent of the production of melatonin in the pineal gland. Melatonin production is determined by the cycle of light and dark as sensed by our eyes, and by our internal body clock - the suprachiasmatic nucleus of the hypothalamus. There are other timing circuits in the brain, which may also contribute.

Remember that neurons are arrranged as circuits where the neurons produce their specific neurotransmitter independently of other neurons (in general - there are exceptions such as nitric oxide - which is a retrograde neurotransmitter). Norepinephrine-releasing neurons make dopamine, then make norepinephrine from the dopamine. However, the dopamine is never released. Only the norepinephrine is released. The dopamine production from norepinephrine-releasing neurons is independent of the dopamine production in dopamine-releasing neurons - though the circuits can be arranged to control one another.

The majority (90 percent) of serotonin which can be measured in blood or urine is made in the enteric nervous system (the gastrointestinal nervous system) - which is almost totally independent of our central nervous system. The two can correlate many time. But there are circumstances where they do not correlate, complicating the interpretation of the lab tests, necessitating additional thought or problem solving or correlation with other data to determine what is happening. If one is measuring blood or urine neurotransmitters, is the level reflecting brain levels or is it primarily a enteric nervous system level? It is up to the skill of the practitioner to determine this.

4. The ability to sleep will depend not only on the presence of melatonin (which is a timing signal for sleep, but is not sedative itself), but the balance of inhibitory and excitatory neurotransmitters - which in turn can be influenced by the activities of the hormones and cytokines. And in the big picture, stress - whicn in a simplistic definition is anything that forces a person to get out of bed - influences the production of neurotransmitters, hormones, and cytokines.

For example, if there is a predominance of norepinephrine (a signal from the sympathetic nervous system indicating stress or a fight-or-fight condition, which also determines wakefulness and alertness), or histamine (which helps determine wakefulness), or glutamate (which is involved in synaptic plasticity and learning, which is also the main excitatory neurotransmitter, which can cause cell death in excess), then a person is forced to stay awake as a side effect of the actions of these excitatory neurotransmitters.

Why are these increased? Stress. Hypothyroidism. Adrenal fatigue. Testosterone deficiency. Progesterone deficiency. Estrogen deficiency. Serotonin defiency (as in panic disorder or some depressions). Dopamine deficiency. Excess pro-inflammatory cytokines. Etc.

There are many conditions which may lead to a higher level of excitatory to inhibitory neurotransmitters - which then leads to insomnia. Serotonin is not the only chemical messenger involved.

It is up to the person and their physician to determine what problems are occurring in concert that can lead to the problem. Many times, it is more than a single neurotransmitter, hormone or cytokine. Addressing only one will often lead to no improvement. All of the problems have to be found and solved.

[DAVID]

Originally Posted by marianco

1. I would dispute the assertion that low serotonin is the primary cause of age-related insomnia.

Serotonin, other neurotransmitters, hormones, and immune-system cytokines are highly linked in their production. The nervous system, endocrine system, and immune system form one system, which I call the mind, which is organized like a computer chip circuit - where in place of electrons traveling through wires, chemical messengers travel through a fluid to transport information. There are thousands if not millions of these chemical messengers, which can work in combinations.

This makes the mind much more extremely complex than the best computers (which only use one messenger - the electron, which can transmit only one message (either on or off). There are 1.1 trillion cells in the brain which is the most important organ of the nervous, endocrine, and immune systems. This combined with the billions of other nervous, endocrine, immune system cells makes for an extremely complex information processing system.

The neurons which release serotonin, the neurons which release dopamine, and the neurons which release norepinephrine, etc. exist as separate groups of neurons, which regulate large groups of other neurons. These regulatory neurons are organized as circuits, which can in turn control one another. For example, there are circuits of dopamine-releasing and serotonin-releasing neurons which reduce the release of norepinephrine from the norepinephrine-releasing neurons. Some acetylcholine-releasing neuron circuits can control dopamine-releasing neurons. Etc.

When serotonin is low, there may be other problems contributing to it which may be the more direct factor in causing insomnia.

For example, when thyroid hormone is low (which occurs in up to 40-50 percent of people depending on the country), serotonin production is lowered because thyroid hormone acting on presynaptic serotonin receptors, determines serotonin production. Hypothyroidism can cause insomnia.

When adrenal fatigue is present, norepinephrine production and release is increased to force more output from the adrenal glands. To increase norepinephrine, the brain reduces serotonin production. It is the high norepinephrine levels which keeps the person awake. Further, in adrenal fatigue, the lower production of cortisol prevents cortisol from reducing Corticotropin Releasing Hormone production. Reducing CRH causes a reduction in norepinephrine production.

2. Self-medication with carbohydrates is not the same as taking Paxil.

Paxil is a complex medication which has multiple mechanisms of action. For example, it increases serotonin levels by blocking reuptake. It can block acetylcholine receptors. It can block histamine receptors - which can cause sedation. It can block norepinephrine receptors. It can increase norepinephrine level by blocking reuptake. it can increase dopamine level by blocking reuptake or by increasing serotonin levels near some dopamine neurons, which have a dopamine reuptake transporter which can be blocked by serotonin, etc. It can block Cytochrome P450 2D6. etc.

Why do some people self-medicate with carbohydrates. The answer is that it serves a purpose. What is that purpose? The answer is that the person has difficulty in producing their own carbohydrates (i.e. glucose) from fat or protein because of impaired gluconeogenesis, which can occur with cortisol deficiency, i.e. adrenal fatigue or insufficiency. The presence of cortisol deficiency results in a rise in norepinephrine production and release, which then keeps the person awake.

3. Melatonin deficiency can occur as one ages - as a consequence of the aging brain and difficulty in producing melatonin - not serotonin.

Melatonin is made from serotonin. But the production of serotonin in serotonin-releasing neurons is independent of the production of melatonin in the pineal gland. Melatonin production is determined by the cycle of light and dark as sensed by our eyes, and by our internal body clock - the suprachiasmatic nucleus of the hypothalamus. There are other timing circuits in the brain, which may also contribute.

Remember that neurons are arrranged as circuits where the neurons produce their specific neurotransmitter independently of other neurons (in general - there are exceptions such as nitric oxide - which is a retrograde neurotransmitter). Norepinephrine-releasing neurons make dopamine, then make norepinephrine from the dopamine. However, the dopamine is never released. Only the norepinephrine is released. The dopamine production from norepinephrine-releasing neurons is independent of the dopamine production in dopamine-releasing neurons - though the circuits can be arranged to control one another.

The majority (90 percent) of serotonin which can be measured in blood or urine is made in the enteric nervous system (the gastrointestinal nervous system) - which is almost totally independent of our central nervous system. The two can correlate many time. But there are circumstances where they do not correlate, complicating the interpretation of the lab tests, necessitating additional thought or problem solving or correlation with other data to determine what is happening. If one is measuring blood or urine neurotransmitters, is the level reflecting brain levels or is it primarily a enteric nervous system level? It is up to the skill of the practitioner to determine this.

4. The ability to sleep will depend not only on the presence of melatonin (which is a timing signal for sleep, but is not sedative itself), but the balance of inhibitory and excitatory neurotransmitters - which in turn can be influenced by the activities of the hormones and cytokines. And in the big picture, stress - whicn in a simplistic definition is anything that forces a person to get out of bed - influences the production of neurotransmitters, hormones, and cytokines.

For example, if there is a predominance of norepinephrine (a signal from the sympathetic nervous system indicating stress or a fight-or-fight condition, which also determines wakefulness and alertness), or histamine (which helps determine wakefulness), or glutamate (which is involved in synaptic plasticity and learning, which is also the main excitatory neurotransmitter, which can cause cell death in excess), then a person is forced to stay awake as a side effect of the actions of these excitatory neurotransmitters.

Why are these increased? Stress. Hypothyroidism. Adrenal fatigue. Testosterone deficiency. Progesterone deficiency. Estrogen deficiency. Serotonin defiency (as in panic disorder or some depressions). Dopamine deficiency. Excess pro-inflammatory cytokines. Etc.

There are many conditions which may lead to a higher level of excitatory to inhibitory neurotransmitters - which then leads to insomnia. Serotonin is not the only chemical messenger involved.

It is up to the person and their physician to determine what problems are occurring in concert that can lead to the problem. Many times, it is more than a single neurotransmitter, hormone or cytokine. Addressing only one will often lead to no improvement. All of the problems have to be found and solved.

Marianco, thank you so much for this answer. I understand better the mechanism of serotonin
God bless you

[Andromeda]

Originally Posted by marianco

When adrenal fatigue is present, norepinephrine production and release is increased to force more output from the adrenal glands. To increase norepinephrine, the brain reduces serotonin production. It is the high norepinephrine levels which keeps the person awake. Further, in adrenal fatigue, the lower production of cortisol prevents cortisol from reducing Corticotropin Releasing Hormone production. Reducing CRH causes a reduction in norepinephrine production.

I'm so glad that you bring in all this useful information because I often find with all the points you raise in answering someone elses post you also answer a lot of other peoples problems. Tell me if I've got the following right....

A couple years ago I was discussing neurochemistry with a lay person who knew next to nothing about the neurotransmitters etc. yet he made one comment which in hindsight seems to be the most insightful point of the whole conversation ie: "Adrenaline and Dopamine are all related "
In my particular case I have been trying to find out the reason for my poor energy and lack of sex drive for years now and while I know theres probably a lot more to it than neurochemistry, I am fairly sure I am low on dopamine. Adrenal fatigue has been suggested as the source of my problem, and now it makes sense in light of your point I have quoted above.. Tell me if this explanation is valid....

Low cortisol leading to hypothalamic over emphasis on CRH production leading to high norepinephrine at the expense of Dopamine production. Lower dopamine then leading to lower testosterone and therefore even less adrenaline effectiveness, and a tendency to estrogen dominance exhibited in the form of gynecomastia
Also I recall another post you made recently saying that sexual activity is only something that can take place properly in a 'relaxed' mode of bodily function. Is it possible that excessive NE levels through adrenal fatigue keep my body in a 'non relaxed' state and are thus the source of my poor erections due to vasoconstriction etc.?

I'd love to hear your critique of my above theory - It could be a milestone in figuring out whats going on... and if anyone feels like I'm hijacking a thread please let me know and I'll do this as a private msg with Marianco...

Cheers in advance,

[Matt Muscle]

Originally Posted by Andromeda

I'm so glad that you bring in all this useful information because I often find with all the points you raise in answering someone elses post you also answer a lot of other peoples problems. Tell me if I've got the following right....

Low cortisol leading to hypothalamic over emphasis on CRH production leading to high norepinephrine at the expense of Dopamine production. Lower dopamine then leading to lower testosterone and therefore even less adrenaline effectiveness, and a tendency to estrogen dominance exhibited in the form of gynecomastia
Also I recall another post you made recently saying that sexual activity is only something that can take place properly in a 'relaxed' mode of bodily function. Is it possible that excessive NE levels through adrenal fatigue keep my body in a 'non relaxed' state and are thus the source of my poor erections due to vasoconstriction etc.?

We are indeed very lucky to have him here in this forum.

I would also like to hear his thoughts on this too. Sounds quite logical.

[marianco]

Originally Posted by Andromeda

I'm so glad that you bring in all this useful information because I often find with all the points you raise in answering someone elses post you also answer a lot of other peoples problems. Tell me if I've got the following right....

A couple years ago I was discussing neurochemistry with a lay person who knew next to nothing about the neurotransmitters etc. yet he made one comment which in hindsight seems to be the most insightful point of the whole conversation ie: "Adrenaline and Dopamine are all related "
In my particular case I have been trying to find out the reason for my poor energy and lack of sex drive for years now and while I know theres probably a lot more to it than neurochemistry, I am fairly sure I am low on dopamine. Adrenal fatigue has been suggested as the source of my problem, and now it makes sense in light of your point I have quoted above.. Tell me if this explanation is valid....

Low cortisol leading to hypothalamic over emphasis on CRH production leading to high norepinephrine at the expense of Dopamine production. Lower dopamine then leading to lower testosterone and therefore even less adrenaline effectiveness, and a tendency to estrogen dominance exhibited in the form of gynecomastia
Also I recall another post you made recently saying that sexual activity is only something that can take place properly in a 'relaxed' mode of bodily function. Is it possible that excessive NE levels through adrenal fatigue keep my body in a 'non relaxed' state and are thus the source of my poor erections due to vasoconstriction etc.?

I'd love to hear your critique of my above theory - It could be a milestone in figuring out whats going on... and if anyone feels like I'm hijacking a thread please let me know and I'll do this as a private msg with Marianco...

Cheers in advance,

You are close.

Norepinephrine = Noradrenaline
Epinephrine = Adrenaline.

Norepinephrine (Noradrenaline) and Dopamine are linked. Epinephrine (Adrenaline) is a minor neurotransmitter in the brain.

Norepinephrine is the primary neurotransmitter to signal the occurrence of stress.
Norepinephrine is the primary neurotransmitter of the fight-or-fight part of the nervous system, called the sympathetic nervous system.

In order to increase norepinephrine production and release from the norepinephrine-releasing neurons, the neurotransmitters, which inhibit norepinephrine production, need to be reduced from their respective neurons. These neurotransmitters include serotonin, dopamine, and GABA.

Norepinephrine increases adrenal hormone production by stimulating the release of Corticotropin Releasing Hormone (CRH) from the hypothalamus. CRH then increases Adrenocorticotropic hormone (ACTH) release from the pituitary. ACTH then travels to the adrenal glands to stimulate steroid hormone production - the primary one being Cortisol.

Norepinephrine also triggers a signal that goes through the sympathetic nervous system nerves which travel parallel to the spine. These nerves then trigger the production of Norepinephrine and Epinephrine from the center of the Adrenal Gland. The adrenal gland, itself, is an enlarged ganglion of the sympathetic nervous system.

What is interesting about CRH is that it travels not only to the pituitary to stimulate ACTH production, but it also travels to the rest of the brain, where it stimulates Norepinephrine release.

CRH thus participates in a positive feedback loop - where increased Norepinephrine results in increased CRH - which then increases Norepinephrine release. If this positive feedback loop is not stopped, the stress signal is magnified repeatedly. If not curtailed, this stress signal snowballs and causes panic attacks. If it is stopped, then the stress signal is stopped.

What stops this positive feedback loop is Cortisol. Cortisol produced from the Adrenal glands goes to the hypothalamus and reduces CRH production - a negative feedback loop. The reduction in CRH reduces ACTH and reduces adrenal hormone production. The reduction in CRH also results in a reduction in Norepinephrine release.

In adrenal fatigue, the adrenal glands do not adequately produce Cortisol in response to stress. The lower Cortisol production then fails to stop the CRH-Norepinephrine positive feedback loop, causing a person to be susceptible to any stress, large or small. This results in an almost constant high level of stress. Stress can't be stopped.

The brain responds to the lack of Cortisol from adrenal fatigue - which causes a deficit in glucose production - by increasing norepinephrine production. This ends up further increasing stress levels. It forces the adrenals to work harder, but it also pushes the adrenals further into fatigue.

High norepinephrine levels signal that the person is in a flight-or-fight condition. Sexual function is inhibited. For example, I doubt that any soldier in combat exhibits an erection.

If there is some sexual function, since norepinephrine triggers ejaculation, the already high norepinephrine level makes ejactulation much easier to occur. This causes premature ejactulation.

Since dopamine production is reduced to allow higher norepinephrine production, sex drive can be further reduced by lower dopamine levels.

The lower dopamine levels may also reduce testosterone production.

Testosterone, itself, increases dopamine production in the brain. The reduction in testosterone production also results in a further reduction of dopamine production in the brain, further reducing sex drive.

If the dopamine production is low enough and involves dopamine neurons in the hypothalamus, then prolactin production can increase. Prolactin can then reduce testosterone production, and possibly contribute to gynecomastia - if the prolactin elevation is high enough - which it may not be.

Gynecomastia may occur alternatively when there is a high level of estradiol or when the potency of estradiol is increased by progesterone.

In the scenario of adrenal fatigue, there is lower testosterone production from the adrenal glands themselves. The adrenal glands provide about 5% of total testosterone in men.

The reduction in testosterone results in less estradiol production from testosterone. This and the lowered progesterone production during adrenal fatigue makes it less likely that gynecomastia occurs - in general. This will depend on multiple factors such as the amount of aromatase enzyme a person has - with those using HCG or those with high abdominal fat having a larger amount of aromatase enzyme.

The ability to have an erection depends on numerous neurotransmitters and hormones, not just norepinephrine. Vasoconstriction of the outlet blood vessels from the penis is what allows the filling of blood which causes the erection - the penis being similar to a balloon.

[Andromeda]

Originally Posted by marianco

You are close.

Norepinephrine = Noradrenaline
Epinephrine = Adrenaline.

Norepinephrine (Noradrenaline) and Dopamine are linked. Epinephrine (Adrenaline) is a minor neurotransmitter in the brain.

Norepinephrine is the primary neurotransmitter to signal the occurrence of stress.
Norepinephrine is the primary neurotransmitter of the fight-or-fight part of the nervous system, called the sympathetic nervous system.

In order to increase norepinephrine production and release from the norepinephrine-releasing neurons, the neurotransmitters, which inhibit norepinephrine production, need to be reduced from their respective neurons. These neurotransmitters include serotonin, dopamine, and GABA.

Norepinephrine increases adrenal hormone production by stimulating the release of Corticotropin Releasing Hormone (CRH) from the hypothalamus. CRH then increases Adrenocorticotropic hormone (ACTH) release from the pituitary. ACTH then travels to the adrenal glands to stimulate steroid hormone production - the primary one being Cortisol.

Norepinephrine also triggers a signal that goes through the sympathetic nervous system nerves which travel parallel to the spine. These nerves then trigger the production of Norepinephrine and Epinephrine from the center of the Adrenal Gland. The adrenal gland, itself, is an enlarged ganglion of the sympathetic nervous system.

What is interesting about CRH is that it travels not only to the pituitary to stimulate ACTH production, but it also travels to the rest of the brain, where it stimulates Norepinephrine release.

CRH thus participates in a positive feedback loop - where increased Norepinephrine results in increased CRH - which then increases Norepinephrine release. If this positive feedback loop is not stopped, the stress signal is magnified repeatedly. If not curtailed, this stress signal snowballs and causes panic attacks. If it is stopped, then the stress signal is stopped.

What stops this positive feedback loop is Cortisol. Cortisol produced from the Adrenal glands goes to the hypothalamus and reduces CRH production - a negative feedback loop. The reduction in CRH reduces ACTH and reduces adrenal hormone production. The reduction in CRH also results in a reduction in Norepinephrine release.

In adrenal fatigue, the adrenal glands do not adequately produce Cortisol in response to stress. The lower Cortisol production then fails to stop the CRH-Norepinephrine positive feedback loop, causing a person to be susceptible to any stress, large or small. This results in an almost constant high level of stress. Stress can't be stopped.

The brain responds to the lack of Cortisol from adrenal fatigue - which causes a deficit in glucose production - by increasing norepinephrine production. This ends up further increasing stress levels. It forces the adrenals to work harder, but it also pushes the adrenals further into fatigue.

High norepinephrine levels signal that the person is in a flight-or-fight condition. Sexual function is inhibited. For example, I doubt that any soldier in combat exhibits an erection.

If there is some sexual function, since norepinephrine triggers ejaculation, the already high norepinephrine level makes ejactulation much easier to occur. This causes premature ejactulation.

Since dopamine production is reduced to allow higher norepinephrine production, sex drive can be further reduced by lower dopamine levels.

The lower dopamine levels may also reduce testosterone production.

Testosterone, itself, increases dopamine production in the brain. The reduction in testosterone production also results in a further reduction of dopamine production in the brain, further reducing sex drive.

If the dopamine production is low enough and involves dopamine neurons in the hypothalamus, then prolactin production can increase. Prolactin can then reduce testosterone production, and possibly contribute to gynecomastia - if the prolactin elevation is high enough - which it may not be.

Gynecomastia may occur alternatively when there is a high level of estradiol or when the potency of estradiol is increased by progesterone.

In the scenario of adrenal fatigue, there is lower testosterone production from the adrenal glands themselves. The adrenal glands provide about 5% of total testosterone in men.

The reduction in testosterone results in less estradiol production from testosterone. This and the lowered progesterone production during adrenal fatigue makes it less likely that gynecomastia occurs - in general. This will depend on multiple factors such as the amount of aromatase enzyme a person has - with those using HCG or those with high abdominal fat having a larger amount of aromatase enzyme.

The ability to have an erection depends on numerous neurotransmitters and hormones, not just norepinephrine. Vasoconstriction of the outlet blood vessels from the penis is what allows the filling of blood which causes the erection - the penis being similar to a balloon.

Oooer a wealth of useful information once again.... I might actually get somewhere with this soon!
In my research into adrenal fatigue I started with the basics of adrenal function, and I learnt that ACTH activates both the adrenal medulla (part of adrenals that produce epinephrine and NE) and the cortex (Cortisol and DHEA)
From your response above it seems to be that most ppl with adrenal fatigue suffer primarily fatigue of the cortex while the medulla continues putting out normal NE levels? Is this the case? I thought both would fatigue at a similar rate (generally) ? If not, why...

Additionally, if a person exhibited low salivary cortisol plotted throughout the day, yet they had high progesterone, and DHEA levels, then must they have some sort of enzymatic problem in the creation of cortisol, rather than primary adrenal fatigue?

Cheers

[marianco]

Originally Posted by Andromeda

Oooer a wealth of useful information once again.... I might actually get somewhere with this soon!
In my research into adrenal fatigue I started with the basics of adrenal function, and I learnt that ACTH activates both the adrenal medulla (part of adrenals that produce epinephrine and NE) and the cortex (Cortisol and DHEA)
From your response above it seems to be that most ppl with adrenal fatigue suffer primarily fatigue of the cortex while the medulla continues putting out normal NE levels? Is this the case? I thought both would fatigue at a similar rate (generally) ? If not, why...

Additionally, if a person exhibited low salivary cortisol plotted throughout the day, yet they had high progesterone, and DHEA levels, then must they have some sort of enzymatic problem in the creation of cortisol, rather than primary adrenal fatigue?

Cheers

Norepinephrine secretion from the locus ceruleus of the brain, result in two signals to the adrenal glands.

First, the norepinephrine signal results in an increase in ACTH secretion from the pituitary gland, which travels to the adrenal glands and stimulates adrenal cortex hormone production - the steroid hormones such as Cortisol, DHEA, Progesterone, Testosterone, Aldosterone.

Second, the norepinephrine signal travels down the sympathetic nerves parallel to the spine to the adrenal medulla, where it triggers the production of norepinephrine and epinephrine.

Both parts of the adrenal glands do not fatigue at the same rate. Most people have fatigue of the cortex - which is the part that fatigues first - before the medulla fatigues.

A synonym for adrenal fatigue is "adrenal depletion".

[Andromeda]

Originally Posted by marianco

Norepinephrine secretion from the locus ceruleus of the brain, result in two signals to the adrenal glands.

First, the norepinephrine signal results in an increase in ACTH secretion from the pituitary gland, which travels to the adrenal glands and stimulates adrenal cortex hormone production - the steroid hormones such as Cortisol, DHEA, Progesterone, Testosterone, Aldosterone.

Second, the norepinephrine signal travels down the sympathetic nerves parallel to the spine to the adrenal medulla, where it triggers the production of norepinephrine and epinephrine.

Both parts of the adrenal glands do not fatigue at the same rate. Most people have fatigue of the cortex - which is the part that fatigues first - before the medulla fatigues.

A synonym for adrenal fatigue is "adrenal depletion".

Wow, talk about misconceptions - I thought that all adrenal output was exclusively the result of the Pituitary ---> Adrenal pathway by ACTH! So the locus coreleus is a source itself ....

As to why most people suffer fatigue of the cortex first is there a reason?- Is it because most people are parasympathetic dominant, and therefore the cortex ends up being taxed more frequently out of the two adrenal regions?

By all means tell me if this theory is mistaken too, as I've encountered apparent contradictions. For example, in my research into the ANS I learnt that the parasympathetic nervous system innervates the adrenal cortex (Cort), where as the sympathetic system innervates the medulla (NE) Yet at the same time I read that higher parasympathetic activity means lower cortisol. The only way I can reconcile this is that sympathetic dominance means more NE and therefore more CRH output with the net result being higher Cort. Whereas in parasympathetic dominance the NE is low to begin with because it is only linked to the adrenals by the cortex which means less NE and its subsequent cortisol inducing loop.?
OR, is it the case that in parasympathetic dominance the body usually has more cortisol to start with (before encountering a stressful situation), and therefore the whole locus coreleus activity and emphasis on NE production is usually less?

Keen to hear your thoughts.. I think the implications could be huge given our ability to manipulate the ANS with techniques such as unilateral nostril breathing and diet etc...

Andromeda.

[DAVID]

Originally Posted by marianco

Norepinephrine secretion from the locus ceruleus of the brain, result in two signals to the adrenal glands.

First, the norepinephrine signal results in an increase in ACTH secretion from the pituitary gland, which travels to the adrenal glands and stimulates adrenal cortex hormone production - the steroid hormones such as Cortisol, DHEA, Progesterone, Testosterone, Aldosterone.

Second, the norepinephrine signal travels down the sympathetic nerves parallel to the spine to the adrenal medulla, where it triggers the production of norepinephrine and epinephrine.

Both parts of the adrenal glands do not fatigue at the same rate. Most people have fatigue of the cortex - which is the part that fatigues first - .before the medulla fatigues

A synonym for adrenal fatigue is "adrenal depletion".

that most people have fatigue of the cortex before the medulla fatigues.

For people who have ADD, the prefrontal cortex doesn't work very well. Physician give stimulant to increase DA and NA for this people. Stimulant release DA and NA in the prefrontal cortex. But the paradox this drug deplete the presynaptic NA and you increase adrenal fatigue. I know people who have ADD with adrenal fatigue. The doctor give him ritalin, but It's feel depress and fatigued after only 2 days on this drug. The doctor give him hydrocortisone, testo, thyroid but I have a crash too AFTER only 2 days on ritalin.

I try to understand the pathophysiology of that because it's complex. What happens ?

[marianco]

Originally Posted by Andromeda

Wow, talk about misconceptions - I thought that all adrenal output was exclusively the result of the Pituitary ---> Adrenal pathway by ACTH! So the locus coreleus is a source itself ....

As to why most people suffer fatigue of the cortex first is there a reason?- Is it because most people are paras