Receptor downregualtion/ upregulation

[jimmyinkedup]

This is a response to a question in my Q@A thread about drug tolerance:

The body has a mechanism that can render drugs inactive. If you think about it anytime you put something in your body you disrupt its normal physiology. The body wants to be in its normal operating range. The Liver specifically expresses a family of enzymes commonly know as the cytochrome P450 oxidases (CYP). This group of enzymes is very diverse and has important functions.
http://forums.steroid.com/newreply.p...eply&p=4325018
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When the body is exposed to a compound lets call it compound X. The body reacts to it by up regulating the expression of CYP that is specific to that compound. CYP will react with compound X rendering it chemically inactive. Usually by oxidizing the compound which is known as Phase I metabolism by pharmacologist. This leads to drug tolerance which requires more drug to get the same therapeutic effect.

http://forums.steroid.com/showthread...=346777&page=5

Glad u posted this as it jarred memory re hormones and this system. Good info and true that about 60% of all drugs are actually removed from our body via this mechanism. Didnt think explaining this was helpful UNTIL remembering that it applies to hormones as well (pretty sure based on female birth control meds(ethynyl estradiol) being removed via this mechanism) Only approx 6 specific cyp enzymes are responsible from removing drugs from the human system and 75-80% of all drugs that are removed via this mechanism are removed by 2 very specific cyp enzymes (sure u know fam/subfam /gene classification system)..then onto detox phase(aka phase 2). In retrospect as I said I rembered hormones are in fact removed via this mechanism (im 90 % sure-jump in if im wrong) SO the million dollar question IS how long will the cyp enzyme remain present after cessation of introduction exogenous test (or other anabolics) causing downregulation in receptor responsiveness? With most drugs longer term use results in longer term downregulation in recptor responsiveness. Based on that ..id hypothesize (and do) that the longer the cycle the longer it would take for upregulation of recpetor responsiveness.

[MuscleScience]

Glad u posted this as it jarred memory re hormones and this system. Good info and true that about 60% of all drugs are actually removed from our body via this mechanism. Didnt think explaining this was helpful UNTIL remembering that it applies to hormones as well (pretty sure based on female birth control meds(ethynyl estradiol) being removed via this mechanism) Only approx 6 specific cyp enzymes are responsible from removing drugs from the human system and 75-80% of all drugs that are removed via this mechanism are removed by 2 very specific cyp enzymes (sure u know fam/subfam /gene classification system)..then onto detox phase(aka phase 2). In retrospect as I said I rembered hormones are in fact removed via this mechanism (im 90 % sure-jump in if im wrong) SO the million dollar question IS how long will the cyp enzyme remain present after cessation of introduction exogenous test (or other anabolics) causing downregulation in receptor responsiveness? With most drugs longer term use results in longer term downregulation in recptor responsiveness. Based on that ..id hypothesize (and do) that the longer the cycle the longer it would take for upregulation of recpetor responsiveness.

I actually asked a toxicologist this question the other day, as far as how long CYP is expressed for a particular drug. I asked him if there was a residual memory say if you took a drug for however long and then stopped and did not retake it again for a long period of time. If CYP would be expressed or upregulated faster much like the immune system does for pathogens and antibody expression.

He told me there was no residual memory and the length of time for CYP to be de-expressed in a cell was dependent on how much of the drug had been used and for how long. He explained in general it only takes a few weeks for CYP expression to return to normal after cessation of a drug regime such as typically prescribed by an MD for short term conditions.