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I knew it.
Remember how my endocrinologist dismissed Addison's out of hand because I don't exhibit hyperpigmentation?
Pigmentation in all non-redheads is the production of eumelanin by melanocytes, triggered by the gene MC1R which is expressed in binding melanotropin to the melanocyte.
ACTH and melanotropin are both products of the proopiomelanocortin (POMC; 176830) gene.[1] Leftover ACTH can be broken down in the blood, and one of the pieces is free melanotropin, ready to bind to the MC1R,[2] which is why excessive ACTH in primary Addison's disease causes hyperpigmentation.[3]
BUT...
Redheads don't express eumelanin, but pheomelanin[4, 5, 6], which is NOT produced by the above chain, in fact, pheomelanin production is turned *off* by the triggering of eumelanin[6], and the MC1R receptor site in redheads is generally dead of any activity. [4][5] Therefore the presence of melanotropin won't activate the melanocytes. It's the whole reason we *ARE* redheads.
So excess ACTH *won't* cause hyperpigmentation in redheads.
Dipshit.
Great. I'm still doing homework for the slow ones. Twenty minutes with Google, skimming articles and putting the pieces together. It took me longer to write this.
Biblio:
1) http://www3.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=155555
2) Nat. Genet. 11: 238, 1995
3) http://www.emedicine.com/DERM/topic761.htm
4) J. Inv. Derm. 117: 1314, 2001
5) Hum. Mol. Genet. 9: 2531, 2000
6) Barsh, G.S. (1996) The genetics of pigmentation: from fancy genes to complex traits. Trends Genet., 12, 299–305.
Pigmentation in all non-redheads is the production of eumelanin by melanocytes, triggered by the gene MC1R which is expressed in binding melanotropin to the melanocyte.
ACTH and melanotropin are both products of the proopiomelanocortin (POMC; 176830) gene.[1] Leftover ACTH can be broken down in the blood, and one of the pieces is free melanotropin, ready to bind to the MC1R,[2] which is why excessive ACTH in primary Addison's disease causes hyperpigmentation.[3]
BUT...
Redheads don't express eumelanin, but pheomelanin[4, 5, 6], which is NOT produced by the above chain, in fact, pheomelanin production is turned *off* by the triggering of eumelanin[6], and the MC1R receptor site in redheads is generally dead of any activity. [4][5] Therefore the presence of melanotropin won't activate the melanocytes. It's the whole reason we *ARE* redheads.
So excess ACTH *won't* cause hyperpigmentation in redheads.
Dipshit.
Great. I'm still doing homework for the slow ones. Twenty minutes with Google, skimming articles and putting the pieces together. It took me longer to write this.
Biblio:
1) http://www3.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=155555
2) Nat. Genet. 11: 238, 1995
3) http://www.emedicine.com/DERM/topic761.htm
4) J. Inv. Derm. 117: 1314, 2001
5) Hum. Mol. Genet. 9: 2531, 2000
6) Barsh, G.S. (1996) The genetics of pigmentation: from fancy genes to complex traits. Trends Genet., 12, 299–305.
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Oh, and FYI, given what I've seen on the addision's mailing list, at least a third (and possibly as much as 3/4th) of all endos are idiots. And even my good endo totally blew me off and was completely convinced I wasn't sick (it was all in my mind after all) until the timed stim test came back. Then it was all "well, of course you do seem to have it. I knew it all the time" on the phone.
In good news, the drugs are helping... mostly. *hugs*
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Far and away the best online resource. Be forwarned though, huge number of post and lots of whinning, but the guy that wrote that great UK website on the topic (the one with the survey) moderates and responds a great deal. Lots of people posting test results and comiserating about the frustrations of endos.
And as far as getting docs to listen... no idea. Z reminded me that the progression you're currently in the middle of is almost exactly the progression I went though. It was incredibly frustrating, but since I'd had a bizzare stim test in the hosptial the endo eventually had to give me one in his office. It was a horrible experience, but it did happen. And 3 days later he calls me cell and says "well... um... I got your test results, and.. um..."
The trick now is finding the right balance/timing/dosages for all the meds. And now there's the theroy that with my system closer to stable I'm now loosing Magnesium, which would explain the really horrible 10 days or so I'm having a month with the wierd cramping...
The best thing the list has taught me is that life can be normal but that it's an adjustable system that needs to be well monitored. Overall though I'm feeling so much better I can't believe how horrible I felt for how long. :) Remember, there is hope. :)
Awesome
Thanks. :)