Help please! ACTH question right before test

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Yes I am taking my test VERY shortly. I just got a question on UWorld that states ACTH is what directly causes skin pigmentation even if it is secreted ectopically (i.e. small cell lung cancer). However, I had always learned that only ACTH secreted from the pituitary can cause this because it is the splitting of POMC that also releases ACTH and that was one way you could differentiate b/w pituitary ACTH and ectopic ACTH secretion.

Please somebody tell me which it is because it is test time in a few hours. Thank you so much

http://www.ncbi.nlm.nih.gov/pubmed/222080

Not sure if this well help, but according to this it seems ectopic ACTH can cause hyper pigmentation, but might be more common in pituitary ACTH.

Dont take my word on this, someone with a little bit more knowledge might be more helpful...anyone confirm this?

BTW good luck! dont freak out, u'll be fine!

Originally Posted by kaleerkalut

Yes I am taking my test VERY shortly. I just got a question on UWorld that states ACTH is what directly causes skin pigmentation even if it is secreted ectopically (i.e. small cell lung cancer). However, I had always learned that only ACTH secreted from the pituitary can cause this because it is the splitting of POMC that also releases ACTH and that was one way you could differentiate b/w pituitary ACTH and ectopic ACTH secretion.

Please somebody tell me which it is because it is test time in a few hours. Thank you so much

I'm pretty sure ectopic ACTH can cause hyperpigmentation. ACTH/MSH can share a similar structure so overproduction of ACTH can cause production of subunits with MSH activity. The main way you differentiation ectopic ACTH vs other is through the dexamethesone suppression test...not through clinical signs of hyper pigmentation.

See Wiki below. Good picture of POMC structure that gives you an idea of where everything comes from. It produces beta-MSH separately from B-lipoproteins. You can also see that ACTH actually has an alpha-MSH subunit (which is cleaved after ACTH production to activate melanosomes), which is the more active regulator of skin hyperpigmentation. I think this can be degraded both in the pituitary and elsewhere to form alpha-MSH, so it doesn't matter where the ACTH is coming from.

http://en.wikipedia.org/wiki/Melanoc...lating_hormone

Generally though, I think small cell tumors are caught before symptoms of prolonged hyperpigmentation develop. But, it doesn't mean they can't.

His question is whether the cleaving hormones prohormone convertases PC1 and PC2 and other peptidases would exist in a small cell carcinoma.

And the answer seems to be "probably".

That, plus ACTH having aMSH subunits, and the fact that keratinocytes release aMSH in response to UV light stimulation to stimulate melanocytes leads to me thinking that these convertases aren't exclusive to the AP.