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| Author | Topic: Intelligent Question #1 | ||
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Elite Bodybuilder 
Posts: 724 |
This board has been criticized in the past for a lack of intelligent questions (and copious amounts stupid, redundant ones)and as a result, a the new Elite Select board was created. So I am going to start a series of questions on this board that, in my opinion, are intelligent. ( But more importantly to me, they are questions to which I'd like answers  ). These questions are not designed to be profound or thought provoking to everyone. Indeed, those with the proper background and experience may find them mundane. It is to those people that I say, here is the opportunity to teach us. And if you don't have a solid, scientific based answer, throw out your theories and let them be disected and criticized. I think a forum for intelligent discussion is what we all want.So let's test the intellect of our Elite members and get the ball rolling. Question #1: If there is only one androgen receptor, common to all cells, then why does the same molecule (e.g. DHT) have different binding efficiencies in different tissues (e.g. skeletal muscle vs. prostate)?     | ||
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Elite Bodybuilder
Posts: 724 |
Maybe there are different protein conformations that act as the androgen receptor in different tissues. | ||
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Amateur Bodybuilder 
Posts: 121 |
bump, I would like to know as well | ||
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Elite Bodybuilder
Posts: 671 |
I disagree with the fact there is an androgen receptor common to all cells. If there were then anabolics used for muscular hypertrophy would also be enlarging tissues such as intestines and heart and lung. ------------------ [This message has been edited by jersey boy (edited October 14, 2000).] | ||
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Amateur Bodybuilder
Posts: 219 |
it is not due to the receptor that makes the androgen molecule work....it is the genetic material <DNA> of the specific tissue that the androgen receptor is in that determines the effects seen from the presence of androgen moecules. DNA in specific tissues are identical to any other tissue's DNA except for a minor <actually major> detail: there are certain parts of the DNA in specific tissues that are not active, i.e. turned "off". the parts of the DNA that are turned "on" are what determines what kind of tissue is going to be made. there is plenty of information on the internet discussing transcription of DNA into the RNAs and translation of RNAs into specific proteins. the "androgen receptor" is merely a spot on the genetic material that has room for an androgen molecule to fit into. the androgen molecule is basically turning "on" the genes to translate proteins from the RNA, meaning that it turns on the production of skeletal muscle proteins, and a long list of other functions ------------------ | ||
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Guru 
Posts: 2076 |
Nice..... | ||
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Elite Bodybuilder
Posts: 742 |
Very thought provoking...........great! ------------------ | ||
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Elite Bodybuilder
Posts: 724 |
Pharm Animal, That was useful information. But you explained what happens after a molecule binds to the AR. I want to know why DHT has a strong binding affinity to the AR in the prostate and a lower binding affinity for the AR in skeletal muscle, if it is indeed the same AR. | ||
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Cool Novice 
Posts: 15 |
some body took fresh bio.I enjoyed that class also.Very interesting stuff,The monk was the man. | ||
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Pro Bodybuilder 
Posts: 566 |
I'm not going to get into the chemical kinetics for enzymatic reactions, binding proteins, and conformational changes because that would just confuse all the non-science guys, so I'll keep it simple. Pharm Animal gave a good description of the mechanism by which a molecule binds to a receptor to cause transcription and translation. But all you really have to know in this situation is that the prostate has more receptors specific to DHT than anywhere else in the body. You have specific body parts that grow like weeds with minimal effort, but others that refuse to grow hardly at all. It's the same principle as the prostate....the muscles that grow have a very high number of hormonal receptors. | ||
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Elite Bodybuilder
Posts: 724 |
O.K. I think I am finally getting it. It comes down to definitions I guess. My lay definition of binding affinity was the 'tendency of one molecule to bind to another'. I now believe this is not what is meant by binding affinity. I guess it is really the association rate of the 2 molecules binding. Of course if the concentration of one molecule (the AR) is greater in one type of tissue than in another, the association rate (= binding affinity) will be higher in that tissue. So, to summarize, binding affinity is greater when the number of androgen receptors are greater. Because different tissues have different numbers of AR's, they will have different binding affinities for the same drug. Do I finally have it? | ||
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Amateur Bodybuilder
Posts: 219 |
i think i need a review of the actual androgen receptor in various tissues and androgen molecule affinities to give a further explanation...i'll post something soon ...in the meanwhile, i'm sure bchemist can definately outdo me ------------------ | ||
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Pro Bodybuilder
Posts: 446 |
from some old research i did: The rate limiting factor in this process appears to be the cytoplasmic concentration of the receptor, rather than the concentration of the steroid or translocation of the complex. The presence of the androgen receptor indicates a tissue is androgen sensitive, and it's concentration gives an indication of how sensitive. The receptor is present in a number of organs, including skeletal muscle. Skeletal muscle typically contains 0.5-3 femto (1E-12) moles per milligram of protein, while other androgen sensitive organs, like the prostate gland, may have up to 25 times more receptors. | ||
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Elite Bodybuilder
Posts: 724 |
Exactly. My original thinking was that 'a' molecule of DHT is 'more likely' to bind to 'an' AR in tissue A vs. tissue B, is what was meant by binding affinity. My new thinking is that 'more' DHT will be taken up in cells of tissue A by androgen receptor's' (because there are more of them), is what is meant by binding affinity. | ||
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Cool Novice
Posts: 36 |
i failed freshman bio....haha...so this shit is way over my head.....just tell me this....what works the best??? shaw | ||
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Pro Bodybuilder
Posts: 405 |
This topic will most definately be over the heads of many of the non-science members, and in reality will not affect the price of rice in China. There is one androgen receptor (AR) and it is activated by the two endogenous androgens, testosterone (T) and DHT (there is more than one isoform of the AR, but this is getting into the realm of receptor physiology that I am not read up on). DHT stabilizes the AR better than T and thus confers a stronger signal in terms of androgenic effects. Also, the tissue type in question modulates the effects of the androgens, since various tissues express different factors that affect the hormones. The prostate expresses high concentrations of 5-alpha reductase (5AR), which converts T into DHT, while the muscles express little 5AR. This explains the different effects seen in each tissue due to the same hormone, T. Each tissue type also expresses different concentrations of AR's, thus changing the sensitivity to the androgens. The tissues also modulate androgen effects through the genetic level. Certain tissues contain different response elements (genetic sequences) that modulate the expression of end-products. As for the concept of binding affinity, this has to do with the "affinity" of the chemical with it's receptor, and not with the concentration of receptors present. A good example is that of clen vs. albuterol. Clen binds the beta-2 receptor at microgram doses and elicits a measurable effect, as opposed to albuterol which requires MILLIgram quantities to give the same response. Therefore clen has a greater relative binding affinity than albuterol. This process is dependant on the electrical nature of the chemical's structure and the electrical nature of the receptor's binding domain. A good overview of the androgen receptor can be found at: http://www.bioscience.org/1996/v1/d/keller1/htmls/59-71.htm [This message has been edited by cockdezl (edited October 15, 2000).] | ||
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Elite Bodybuilder
Posts: 724 |
Dammit, Cockdezl, just when I thought I had it figured out .O.K. So binding affinity has nothing to do with concentrations of AR's. It was what I originally thought it was. What I was missing was the term 'relative', which you have brought to my attention. The drug can have different relative binding affinities in different tissues because of the different accessory proteins. O.K. It is all starting to make sense now.
quote: True that the dose-response relationship is due in part to the relative binding affinity of the 2 substances. But it is also due in part to the efficiency with which the drug-receptor interaction is coupled to the response as well as each drugs metabolism and pharmacokinetics. | ||
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Moderator
Posts: 5148 |
AnabolicumMister think of binding affinity the same way one looks at electron afffinity in atoms. Or for an example you can think of hemoglobin, if your hemo has CO (carbon monoxide) available it will always pick it up instead of O2(oxygen). That is to say that if both molecules are present your hemo will always choose the CO over the O2. So we say that the hemo has a higher affinity for the CO. Similarly some chemical molecules have a higher affinity for certain receptors, if both molecules are present one will be 'more attracted' to the receptor, or vice versa. So that molecule will be picked up. As well you have to look at how well it activates the receptor, as you can have chemicals with high binding affinities but all they do is antagonize the receptor. ie clomid and novaldex which actually block estrogen receptor sites and are in fact weak estrogens themselves with high binding affinities, but they don't exert the same effect as the estrogen in your body. Did I help? ------------------ | ||
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Amateur Bodybuilder
Posts: 290 |
I'm bumping this, 'cause as an English major and still pretty much new to this sh*t, this is very good readin', although I have no idea what half of it is saying! Thanks Anabolicum Mister, keep 'em comin'! ------------------ |
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posted October 14, 2000 12:40 PM