Corticotropin releasing hormone, the hypothalamus, and endorphins

[Kdem]

In a nutshell: does anyone know about this ? I know about the various axes like HPA, HPT, HPG, HPI (details unknown to me). Endocrinology is almost my hobby ...

Here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3104618/#__sec2title

(maybe some of you will like that article)

'Beta-endorphins are primarily synthesized and stored in the anterior pituitary gland² from their precursor protein proopiomelanocortin (POMC). However, recent studies suggest cells of the immune system are also capable of beta-endorphin synthesis because immune cells possess mRNA transcripts for POMC³ and T-lymphocytes, B-lymphocytes, monocytes and macrophages have been shown to contain endorphins during inflammation.^4–6POMC is a large protein that is cleaved into smaller proteins such as beta-endorphin, alpha-melanocyte stimulating hormone (MSH), adrenocorticotropin (ACTH), and others. The pituitary gland synthesizes POMC in response to a signal from the hypothalamus; that signal being corticotroponin-releasing hormone (CRH). The hypothalamus releases CRH in response to physiologic stressors such as pain, as in the postoperative period. When the protein products of POMC cleavage accumulate in excess, they turn hypothalamic CRH production off - that is, feedback inhibition occurs.'

Which could be why I get that setback one or two days after taking an opiate, which appears to resolve only after exercise. (As I mention in http://www.bluelight.org/vb/threads...(-)-have-given-me-a-sky-high-opiate-tolerance which may not really be due to clonazepam itself ?)

It appears that proopiomelanocortin is synthsized from pre-pro-opiomelanocortin (https://en.wikipedia.org/wiki/Proopiomelanocortin) but I was unable to find where that was synthesized from. Is there a formal 'axis' like HPA, HPT etc. ?

 

[Kdem]

And as a follow up, interactions between opiates (I did not check for natural endorphins) and the HPA axis do exist. Well, I sort of said that in the previous post. There is another thread here about corticosteroids ... (mostly the same)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1821355/ 'Opiates suppress the hypothalamic-pituitary adrenal (HPA) axis, whereas cocaine leads to HPA activation.'

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3965279/ 'We conclude that his morphine therapy had caused profound suppression of his HPA and pituitary–gonadal axes and suggest that clinicians should be aware of these significant changes in patients on even short-term opiate therapy.'

http://www.medscape.com/viewarticle/840537_3 'An emerging topic of concern regarding chronic opioid use is its effect on adrenal function. Opioids appear to have inhibitory effects on adrenocorticotropic hormone (ACTH) and adrenal cortisol secretion in both acute and chronic settings, primarily resulting in secondary adrenal insufficiency.'

'Patients diagnosed with opioid-induced adrenal insufficiency should be treated with replacement glucocorticoids until they are weaned off opioids and adrenal axis recovery is confirmed.'

http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2012.01918.x/pdf

 

[sekio]

I don't think opioid receptor activation is what causes suppression of beta-endorphin/POMC production (it may be the protienacious endorphin degradation products), but I could be wrong. Otherwise nobody would use opioids lest the rebound pain drive them nuts; stuff like anesthetic doses of fentanyl would be terror for the natural endorphin system.

I'm pretty sure that in chronic opioid addiction, B-endorphins are still made and distributed as normal, the end receptors just aren't around to bind it. (ref: naloxone/naltrexone on a person in opiod w/d just makes them worse)