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
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
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.