HPA Axis and MS

If it's on your mind and it has to do with multiple sclerosis in any way, post it here.

HPA Axis and MS

Postby OddDuck » Fri Feb 11, 2005 12:25 pm

Here is something new and interesting (at least I don't recall having seen it before).

Deb

http://www.neurology.org/cgi/content/abstract/53/4/772



Dysregulation of the hypothalamo-pituitary-adrenal axis is related to the clinical course of MS

F. Then Bergh, MD, T. Kümpfel, MD, C. Trenkwalder, MD, R. Rupprecht, MD and F. Holsboer, MD, PhD

From the Max Planck Institute of Psychiatry, Neurology, Muenchen, Germany.

Address correspondence and reprint requests to Dr. Florian Then Bergh, Neurologische Klinik, Klinikum Grosshadern, Marchioninistr. 15, D-81377 Muenchen, Germany.

OBJECTIVE: To investigate whether dysregulation of the hypothalamo–pituitary–adrenal (HPA) axis is related to clinical characteristics in MS.

METHODS: The authors performed the combined dexamethasone–corticotropin-releasing hormone test (Dex-CRH test) in 60 MS patients and 29 healthy control subjects. In addition, the short adrenocorticotropic hormone (ACTH) test was performed in 39 consecutive patients. All patients had active disease and none were treated with glucocorticoids, immunosuppressants, or immunomodulators.

RESULTS: The patients had an exaggerated rise in plasma cortisol concentrations in the Dex-CRH test (p < 0.05), indicating hyperactivity of the HPA system. The degree of hyperactivity was moderate in relapsing–remitting MS patients (n = 38; area under the time-course curve for cortisol [AUC-Cort] 226.2 ± 38.9 arbitrary units [AU], mean ± SEM), intermediate in secondary progressive MS patients (n = 16; AUC-Cort, 286.8 ± 60.2 AU), and marked in primary progressive MS patients (n = 6; AUC-Cort, 670.6 ± 148.6 AU). Differences were significant between the three patient groups (p < 0.005), and between control subjects (n = 29; AUC-Cort, 150.8 ± 34.1 AU) and each patient group. Indicators of HPA axis activation correlated with neurologic disability (Kurtzke’s Expanded Disability Status Scale), but not with the duration of the disease, number of previous relapses, previous corticosteroid treatments, or depressed mood (Hamilton Depression Scale). The ACTH test was normal in 31 of the 33 patients studied.

CONCLUSION: HPA axis hyperactivity in MS is related to the clinical type of disease, with a suggestion of increasing HPA axis dysregulation with disease progression.

Key words: MS—Hypothalamo-pituitary-adrenal axis—Dexamethasone-CRH test.
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Postby bromley » Fri Feb 11, 2005 12:43 pm

OddDuck,

Please can you, if possible, translate this into something which means something to the average person. hypothalamo–pituitary–adrenal (HPA) axis? From my biology 'o' level I recall that pituitary and adrenal are glands (but I failed my 'o' level biology and it was 24 years ago).

Any thoughts on what this means in terms of a possible cause (or is it just a reaction to having ms?)? Is it something which could be treated?

Can dysregulation be regulated?

What interests me (not actually knowing anything about the subject) is that the results (for a change) actually appear to show a distinct pattern / association.

Sorry for putting it back to you, but I look at you as a bridge between the scientifc world and those of us more on the 'arts' side.

Does your treatment regime link into this at all?

Sorry for all the questions, but I like to think you are busy at the weekend.

All the best

Bromley
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Postby OddDuck » Fri Feb 11, 2005 2:02 pm

Hi, bromley!

Ok.........I'll do my best.

First, I want to point out that what is interesting in the above, is the fact that ACTH tended to remain within normal limits in this study and correlation, even though the HPA axis was "hyper". THAT is interesting (and there is no answer for, that I know of). This is just a point to keep in mind. Intriguing avenue for some researcher to go down, isn't it?

The HPA axis does consist of the hypothalamus, pituitary and the adrenals.


The hypothalamus: "...the hypothalamus is a region of the brain located below the thalamus, forming the major portion of the ventral region of the diencephalon and functioning to regulate certain metabolic processes and other autonomic activities. The hypothalamus links the nervous system to the endocrine system by synthesizing and secreting neurohormones often called releasing hormones because they function by stimulating the secretion of hormones from the anterior pituitary gland — among them, gonadotropin-releasing hormone (GnRH). The neurons that secrete GnRH are linked to the limbic system, which is very involved in the control of emotions and sexual activity. The hypothalamus is also the area of the brain that controls body temperature, hunger and thirst, and circadian cycles. The hypothalamus connects to the pituitary gland via the tuberoinfundibular pathway."

The pituitary gland:
"The pituitary gland, or hypophysis, is an endocrine gland about the size of a pea that sits in the small, bony cavity (sella turcica) at the base of the brain. Its posterior lobe is connected to a part of the brain called the hypothalamus via the tuberoinfundibular pathway. The anterior pituitary lobe receives releasing hormones from the hypothalamus via a portal vein system. The pituitary gland secretes hormones regulating a wide variety of bodily activities, including trophic hormones that stimulate other endocrine glands. For a while, this led scientists to call it the master gland, but now we know that it is in fact regulated by releasing hormones from the hypothalamus. It is physically attached to the brain by the pituitary, or hypophyseal, stalk connected with the median eminence.

The pituitary gland is divided into two sections: the anterior lobe (adenohypophysis) and the posterior lobe (neurohypophysis). The posterior pituitary is, in effect, a projection of the hypothalamus. It does not produce its own hormones, but only stores and releases the hormones oxytocin and antidiuretic hormone (ADH).

The anterior pituitary secretes growth hormone, prolactin, follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, endorphins and other hormones.

There is also an intermediate lobe in many animals. In adult humans it is just a thin layer of cells between the anterior and posterior pituitary, nearly indistinguishable from the anterior lobe. The intermediate lobe produces melanocyte-stimulating hormone (MSH), although this function is often (imprecisely) attributed to the anterior pituitary."

The adrenal glands: "In mammals, the adrenal glands (also known as suprarenal glands) are the triangle-shaped endocrine glands that sit atop the kidneys. They are chiefly responsible for regulating the stress response through the synthesis of corticosteroids and catecholamines, including cortisol and adrenalin."

The HPA axis is also closely related to autonomic functions. Dysfunction of the HPA axis has been shown to be associated with alzheimers, HIV, depression, cognition, autoimmune disorders such as rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis and Sjögren’s Syndrome, just to name a few. And now, it looks like maybe some patterns of MS, also. :?:

The description of the HPA axis that I'm going to post here appears on the surface to be a little unrelated to what seems to happen to people with MS, doesn't it? I'm wondering if there isn't something more about the HPA axis itself that may yet need to be learned that isn't known right now. :?: :idea:


DEFINITION OF THE HPA AXIS (excerpts):

Hypothalamic-pituitary-adrenal axis
From Wikipedia, the free encyclopedia.

The hypothalamic-pituitary-adrenal axis (HPA axis) is a major part of the neuroendocrine system that controls reactions to stress. Species from humans to the most ancient organisms share components of the HPA axis. It is the mechanism for a set of interactions among glands, hormones and parts of the mid-brain that mediate a general adaptation syndrome.
Anatomy


The HPA axis includes parts of the hypothalamus, the anterior lobe of the pituitary gland, the adrenal cortices, hormones, systems that transport hormones and feedback mechanisms that transport cortisol from adrenal glands back to the hypothalamus and to other parts of the brain.

The hypothalamus releases corticotropin-releasing factor (CRF) from an area along the median eminence. The hormone is transported to the anterior lobe of the pituitary through the portal blood vessel system of the hypophyseal stalk, which descends from the hypothalamus. In the anterior pituitary gland, CRF stimulates release of stored adrenocorticotropic hormone (ACTH), which is transported by the blood to the adrenal cortex of the adrenal gland, where it rapidly stimulates biosynthesis of corticosteroids from cholesterol.

Function

Release of CRF from the hypothalamus is influenced by stress, by blood levels of cortisol and by the sleep/wake cycle.

Anatomical connections between amygdala, hippocampus, and hypothalalamus facilitate activation of the HPA axis. Sensory information arriving at the lateral aspect of the amygdala is processed and conveyed to the central nucleus, which hosts projections to several parts of the brain in involved responses to fear. At the hypothalamus, fear-signaling impulses activate both the sympathetic nervous system and the modulating systems of the HPA axis.

Increased production of the glucocorticoid cortisol mediates alarm reactions to stress, facilitating an adaptive phase of a general adaptation syndrome in which alarm reactions are suppressed, allowing the body to attempt countermeasures.

Glucocorticoids serve important functions including modulation of stress reactions but they can be damaging. Atrophy of the hippocampus in humans and animals exposed to severe stress is believed to be caused by the presence of excessive stress-induced glucocorticoids. Deficiencies of the hippocampus are believed to reduce the memory resources available to help a body formulate appropriate reactions to stress.
...

Research

Researchers have focused on the effects of monoamine neurotransmitters in regulating the activity of the HPA axis, especially dopamine, serotonin and norepinephrine. ....

Neurochemistry and physiology

The general neurochemistry of the general adaptation syndrome is now believed to be well understood, although much remains to be discovered about how this system interacts with others in the brain and elsewhere in the body. ....


Bromley's questions:

Any thoughts on what this means in terms of a possible cause (or is it just a reaction to having ms?)?


It could go either way.

But, I might suspect that if you were to ask the researchers in the Netherlands, they "might" refer you back to their ongoing research into norepinephrine dysfunction as being integral. THEY tend to lean toward that being a "causal factor" in MS. Of course, no one knows for certain - yet. And their theories may only pertain to certain "patterns" of MS. MS could be caused from several different things or consist of different and separate pathogeneses altogether (referring back to Dr. Claudia Lucchinetti's work).

In any event, maybe the question here should be: Is it possible that we can at least drastically slow down the progress to disability if we regulate the HPA axis?


Is it something which could be treated?


Most likely, yes!

Can dysregulation be regulated?


Yes.

What interests me (not actually knowing anything about the subject) is that the results (for a change) actually appear to show a distinct pattern / association.


That interested me, also, bromley. It appears it was a pretty "clean" study, wasn't it?

Does your treatment regime link into this at all?


I'll take the liberty to rephrase this a little bit. Does desipramine (for one) appear to be a strong candidate to study, if the above holds true? Absolutely, yes.

Deb
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Postby Arron » Fri Feb 11, 2005 2:22 pm

Another great finding and explanation, Deb. Thank you.
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Postby bromley » Fri Feb 11, 2005 2:41 pm

Deb,

Thanks - I'll let you have the rest of the weekend off.

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Postby OddDuck » Fri Feb 11, 2005 2:57 pm

:lol:

Oh, you know me, bromley!!! I'm sure you'll see more of me anyway!

(By the way, I hope all is well with you!!)

Best always!!

Deb
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Postby OddDuck » Fri Feb 11, 2005 2:58 pm

You're welcome (and thank you, too, Arron!)

Deb
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Postby OddDuck » Fri Feb 11, 2005 3:46 pm

Well, here I go.......on another "search".

Here's something recent (and for heavens sake - I swear I didn't notice this until I just now copied it here - it's from the Netherlands!). Now what is really good about this, (although it may be sort of gross), is it comes NOT from educated "guesses" by researchers, but from examination of ACTUAL brains and CFS of MS patients postmortem!!!:

Annals of the New York Academy of Sciences 992:118-128 (2003)
© 2003 New York Academy of Sciences

The Hypothalamo-Pituitary-Adrenal Axis in Multiple Sclerosis
INGE HUITINGA, ZEYNEL A. ERKUT, DENIS VAN BEURDEN and DICK F. SWAAB
Netherlands Institute for Brain Research, Amsterdam, the Netherlands

Address for correspondence: Inge Huitinga, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam, the Netherlands. Voice: +31-20-5665503; fax: +31-20-6961006.
i.huitinga@nih.knaw.nl
Ann. N.Y. Acad. Sci. 992: 118-128 (2003).

During multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS), activation of the hypothalamo-pituitary-adrenal (HPA) axis is considered to modulate the immune system in such a way that the probability of recovery from a relapse is increased. In a series of postmortem studies we observed a significant activation of corticotropin releasing hormone (CRH) neurons and increased cortisol in the cerebrospinal fluid (CSF) of MS patients, indicating activation of the HPA axis in this disease. On the other hand, sepsis, while elevating cortisol in control subjects, did not associate with a further increase of cortisol in MS patients. Thus, the activated HPA-system in MS does not respond to an acute inflammatory stimulus. In order to investigate the role of chronic inflammation in the CNS in the activation of the HPA axis in MS, MS lesions in the hypothalamus were quantified and interleukin (IL)-6 levels in the CSF were determined. There was no difference in IL-6 levels between MS and control patients. A positive correlation was found between cortisol and IL-6 in control subjects with sepsis, but not in MS patients with sepsis or MS and control groups without sepsis. Thus, IL-6 in the CSF of MS patients is not the cause of the activation of the HPA system in MS. We found a remarkably high incidence (95% of the patients) of MS lesions in the hypothalamus, of which the majority (60%) were active. The more active lesions were present in the hypothalamus, the shorter the disease duration to the moment of death, indicative of a worse disease course. Preliminary data show suppression of the activation of CRH neurons by active hypothalamic MS lesions. We propose that this suppression of CRH neurons by active hypothalamic MS lesions causes the concomitant unfavorable disease course via an inadequate cortisol response during relapses of MS.


Ok, that leads us back to the question............what if we keep the HPA axis regulated and the cortisol response balanced in MS?

It appears from this, also, that inflammation (immune response) itself may NOT be the primary culprit, particularly in progressive forms of MS.

I've said it before, and I'll say it again. I personally think the Netherlands guys are onto something with this!!! And I've got the perfect drug to try on it!

Deb
Last edited by OddDuck on Fri Feb 11, 2005 4:08 pm, edited 1 time in total.
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Postby OddDuck » Fri Feb 11, 2005 4:02 pm

Oh, cool! I just NOW found that this isn't entirely "new" to the NMSS, either! (Maybe that is why my theories haven't been totally debunked by them? They've been ahead of me all along? Except I stumbled across the drug agent to try? Oh, cool!)

The only thing is, I don't think it's purely "stress" related. I think there is an actual dysfunction happening, and stress only makes it worse. But that's just my personal opinion, because I keep coming up with the same "theories" as the Netherlands.

At least we are looking into it here in the U.S., too. Great news!!

EXCEPT, the Netherland researchers have found and hypothesized that immune responses for some unknown reason are NOT part of the HPA axis dysfunction or hyperactivity in progressive forms of MS (which of course makes more sense, because most progressive types of MS don't involve inflammation anyway). I think the Netherlands may be ahead of us (?) Personally, I think it will take a drug agent to really help MSers, not just "stress relief". That won't be enough. I think that is way too simplified. And the drug agent I have stumbled upon does a lot more than just provide stress relief (i.e. it does has immune system effects, genetic effects, etc. etc.)

Still this is interesting, although I think this person's approach is way too basic and simplified.

Victoria E. Beckner, PhD
Veterans Affairs Medical Center
San Francisco, CA
NMSS Area: Northern California Chapter
Award: Postdoctoral Fellowship
Mentor: David C. Mohr, PhD

Term/Amount: 9/1/04-7/31/07; $133,825

“HPA: predictor and treatment target for stress-related brain MRI lesions in MS”

Investigating possible links between stress, stress hormones and MS disease activity, and the impact of a stress management program.

People with MS commonly report that stress worsens their symptoms. Stress can cause levels of a hormone called cortisol to increase. Cortisol is produced by a part of the brain called the hypothalamic-pituitary axis (HPA). Researchers suspect that when cortisol is maintained at unnaturally high levels for long periods of time, it can interfere with normal immune responses.

Victoria E. Beckner, PhD, is exploring the possibility that the HPA in people with MS is overactive. She is measuring stress levels in people with the disease for one year using a standard psychological test and biologic measures of stress-related hormones and correlating these results with the number of MS brain lesions (areas of injury) seen with magnetic resonance imaging. She is also testing whether a stress-management program can reduce HPA hyperactivity.

Establishing a biologic basis for the long-suspected relationship between stress and MS, and testing strategies to reduce stress, may result in fewer symptoms and increased quality of life for people with MS.
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Postby OddDuck » Fri Feb 11, 2005 4:15 pm

Well, I could go on and on regarding this issue, because I'm continually finding right now that there has been research into this for some time, all finding the basic same results and reaching the same conclusions.

The bottom line question I have to this, then, is:

If this tends to show itself this often in progressive MS, and there ARE drug agents to try for it, why in the heck hasn't anyone tried it yet??!!!

Well, I'm still pushing for it. :wink:

Stay tuned..............

Deb
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Postby OddDuck » Sat Feb 12, 2005 7:15 am

Ok..........here is something that I throw out to you folks (Sharon, you're our hormone expert.......what have you found about this?):

It has been found that the HPA axis is "hyperactive" in MS, but ACTH stays within normal limits! How in the world can that be happening? But it is.

It's too easy to blame this on "lesions" being the initial cause of the HPA hyperactivity. I don't think that's it. Doesn't make sense. Genetic mutation(s) makes more sense.

In an odd way, it does make sense to discover that ACTH stays within normal limits in MS, though, because if ACTH was involved at all in MS, then the disease itself would either present itself as Addison's or Cushing's, not MS. Right? And for some strange reason, we don't even find Addison's or Cushing's as co-existing with MS!? How odd!!!

And we quickly come back around to norepinephrine again (and our Netherlands friends.) And the HPA axis also helps to explain why statins appear to be helpful in MS, too. The adrenal cortex and medulla. But ACTH isn't involved???

How intriguing!!!!!

Maybe I've missed something. I'm sure I can't be the first to have noticed or posed this question.

Anybody have any comments?

Deb
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Postby OddDuck » Sat Feb 12, 2005 7:31 am

I'm so dumb! Sharon found some of this same research before! Credit and kudos to Sharon!!!

My apologies, Sharon! Good heavens! It didn't even dawn on me that these studies were part of your original questions to the NMSS! Duh, Deb! (Jeez, you must be thinking what an idiot I am right about now, and I don't blame you!) No excuse from me, but I've always just relied on your expertise on the hormone equation of things, that I guess it didn't "connect" right away that you had (of course) already been down this same road! :oops:

Anyway, did you find the ACTH paradox, also? What do you make of that?

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Postby BioDocFL » Sat Feb 12, 2005 7:58 am

OddDuck,

Something I remember from long ago in anatomy class: the hypothalmus is above the pituitary gland and a channel connects them, so the hypothalmus can 'drip' hormones down to the pituitary to stimulate it. The pituitary sits in the sela turcica (Turkish saddle), as you mentioned. On either side of the sela turcica are the internal carotid arteries, they have just entered the skull at the base, and are carrying blood to feed the brain.

Hormones in bulk, including histamine, could get into the blood system there and then go to the body. Immediately after passing the sela turcica, the arteries split, one smaller branch feeds the optic area (eye orbits, bridge of nose, top of cheeks) and the larger branch goes to the top of the head and drains down into the brain.

The branch going to the optic area (maybe it's called the optic artery?) would have a high concentration of whatever (I believe this could include histamine). So the optic area gets a high dose of whatever. Could that be why MSers and Lupies get eye problems? And could it be part of the explanation for the butterfly rash in Lupus? It was one of my many tangent thoughts but I never tried to follow up on what the culprits and consequences might be if in fact there was something like histamine in higher concentration in one area.

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Postby OddDuck » Sat Feb 12, 2005 8:45 am

Hi, Wesley!

Yes........I'm with you. Factor in this, also, though. Genetic transcription takes place in the hypothalamus.

Now, not to get too far off course, but in another thread somewhere around here, I mentioned the eyes. It was at http://www.thisisms.com/modules.php?nam ... opic&t=754 (regarding the transcription factors c-Fos and Zif268).

Something tells me, though, that histamine isn't the avenue to follow. The focus, as Sharon mentions........is cortisol in MS.

Check out: http://arbl.cvmbs.colostate.edu/hbooks/ ... rview.html Flip back and forth in that whole presentation.

Another really good website is: http://users.rcn.com/jkimball.ma.ultran ... #addison's Click in and around in that website, also. Really good info there!

And get this! My speculation above was regarding HPA hyperactivity without abnormal ACTH fluctuations. Look how desipramine "normalizes" HPA hyperactivity without screwing around with ACTH. (Notice also, the mention of naloxone, which is similar to naltrexone - i.e. LDN, and when you consider it deeply, and I hate to say it, but this indicates that LDN might not be the best to take if you have progressive MS.) Interesting..............

This is a little hard to decipher, because it basically is saying that under different physiological conditions, desipramine paradoxically will present a different mechanism of action. The bottom line of what it is saying, though, is that desipramine appears to "hold" the HPA axis functioning at a constant normal level. I'll post a second link after this, that also presents some substantive evidence for desipramine for HPA hyperactivity.

Journal of Clinical Endocrinology & Metabolism, Vol 80, 802-806, Copyright © 1995 by Endocrine Society

ARTICLES

The effect of desipramine on basal and naloxone-stimulated cortisol secretion in humans: interaction of two drugs acting on noradrenergic control of adrenocorticotropin secretion

DJ Torpy, JE Grice, GI Hockings, GV Crosbie, MM Walters and RV Jackson
Department of Medicine, University of Queensland, Greenslopes Hospital, Brisbane, Australia.

Desipramine (DMI), a tricyclic antidepressant and norepinephrine (NE) reuptake blocker, is reported to induce ACTH and cortisol release acutely in humans, probably by facilitating central NE neurotransmission. Tricyclic antidepressant therapy, including DMI, normalizes the ACTH and cortisol hypersecretion that often accompanies depression. The mechanism of hypothalamic-pituitary-adrenal (HPA) axis inhibition by DMI in humans is unknown. In rats, DMI reduces the activity of the locus ceruleus, a major source of NE innervation of the hypothalamic paraventricular nucleus, the site of CRH neurons. Naloxone induces ACTH and cortisol release in humans through a noradrenergic- mediated mechanism and a probable consequent stimulation of hypothalamic CRH release. To study the interaction of these drugs on NE neurotransmission and, hence, HPA axis activity in humans, we administered DMI alone and with naloxone in a randomized, double blind, placebo-controlled protocol in eight healthy male volunteers. DMI (75 mg, orally) was given 180 min before naloxone (125 micrograms/kg BW, i.v.). Plasma ACTH and cortisol were measured at frequent intervals from 60 min before to 120 min after naloxone treatment. Plasma cortisol levels were 77% higher 180 min after DMI compared to those after placebo treatment (287 +/- 17 vs. 162 +/- 14 nmol/L; P = 0.000005). DMI reduced the naloxone-induced rise in cortisol (P = 0.02), but there was no change in the integrated cortisol response. The increase in basal plasma ACTH levels after DMI treatment did not reach statistical significance. DMI significantly increased systolic blood pressure and heart rate consistent with an effect on the noradrenergic control of the cardiovascular system. In summary, DMI increased basal cortisol levels consistent with facilitation of NE neurotransmission and, hence, hypothalamic CRH release. However, DMI had no enhancing effect on naloxone-induced cortisol release. This contrasts with the synergy observed when non-antidepressant agents that increase NE neurotransmission are given with naloxone to humans. DMI increases glucocorticoid feedback sensitivity in the rat HPA axis after several weeks through up-regulation of central corticosteroid receptors. However, this slowly developing effect is unlikely to occur during these acute studies. The effect of DMI on naloxone-induced cortisol release is consistent with an inhibitory effect on central noradrenergic control of ACTH release, perhaps at the locus ceruleus. This is the first human study to suggest an inhibitory effect of DMI on central noradrenergic control of ACTH release.


Again, this next abstract shows how desipramine normalizes the HPA axis. And not only that, but desipramine appears to act very similarly as a steroid, but without a steroid's extreme side effects, etc. Again, normalization (or maintaining balance) of the immune system and inflammatory responses, also. It can be found at:

http://molpharm.aspetjournals.org/cgi/c ... l/52/4/571


EDIT: Wesley, also do a google web search on zif268+hypothalamus. You'll find some interesting stuff on that.
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Postby OddDuck » Sat Feb 12, 2005 10:20 am

Well, shoot. Maybe cortisol isn't the main focus: http://www.medscimonit.com/pub/vol_7/no_5/1683.pdf

This keeps bringing me back around to gene transcription and HPA hyperactivity as it pertains directly to the hypothalamus. The pituitary doesn't seem to be involved (again reiterating ACTH, for one, as normal in MS, even though overall HPA function is hyperactive).

How odd!

There is speculation that HPA hyperactivity is secondary to the brain damage. Something about that doesn't seem right, though. Why so MUCH damage, then, concentrated in the hypothalamus? You would logically surmise that if it was the damage causing the hyperactivity, that you wouldn't necessarily see such a correlation of a high percentage of brain damage taking place in so many people specifically in the hypothalamus in progressive MS.

Something involving the hypothalamus MUST be happening FIRST in order for continuing damage to keep taking place in the same location of the brain. That's only common sense, I'd think!

And again, doesn't that leave us back to gene transcription factors and/or genetic mutations? And norepinephrine.

Ok...................just to switch to causal relationships again, what viral infections (bacterial has been looked at and it didn't correlate) target the hypothalamus directly or the physiological processes that involve the hypothalamus?

hmmmmmmmmmm.............

Deb

EDIT: Ok, so far, it's not HSV (herpes virus), because that affects the pituitary.
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