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.

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.