Food for thought, long read but great question to think about

[MuscleScience]

I sat in on a lecture by a endocrinologist on friday. He talked about receptor up/down regulation and briefly talked about hypogonadic males. In the talked he described two mechanisms for the disorder. One mechanism is the low production or no production of Testosterone from the testis the second is the low sensitivity of the plasma membrane receptors that testosterone binds to to be shuttled into the target cells.

in the first mechanism he explained that the target cells for testosterone have a much higher percentage of AR plasma membrane receptors than that of normal gonadic individuals to absorb what ever amount of testosterone that is circulating in the blood stream. He then explained possible treatments for this particular mechanism with large doses of testosterone. He said that over time the AR receptor concentrations would decrease, which is no suprise. So I asked the question what happens to the receptor concentrations after the discontinuing of HTR. He said that gradually over time that the receptors would increase in density as Testosterone levels in the blood decrease and may actually be higher in some instances if levels of Test drop below baseline for the already low hypogonadic individuals.

Further in the talk when he talked about HTR effectiveness decreasing over time due to the decrease in AR receptor concentration over extended periods of time. He explained that increasing dosages were not the most desirable way because of increase in side effects. Ok so then this brings up a question that for obvious reasons I couldnt ask at the talk.

My question is, if a person isnt overly sensitive to low androgen levels and all the sides that go along with it. is or could it be effective to go a little will with low test levels after a cycle to increase AR levels before PCT begins. Keep in mind I ask this question for normal gonadic individuals after the discontinuance of a steroid cycle.

To me it sounds crazy to do this but I wanted to throw this out to you guys for debate. Now dont flame me for asking this question, I have no answers or specifics on how this method would work. This just popped in my head as I sat through the lecture on friday based on methods he described.

[jagdpanther]

I copied the quote and foot notes below from the following link.

http://forums.steroid.com/showthread.php?t=199833

Testosterone significantly increases the concentrations of the A. R in cells which are critical for muscle repair and growth.(4, 6 )

4 Curr Opin Clin Nutr Metab Care. 2004 May;7(3):271-7.
6 J Clin Endocrinol Metab. 2004 Oct;89(10):5245-55.

I'm not an endocrinologist but I thought that the idea of receptor down regulation or a decrease in receptor concentration while on cycle had been debunked a while ago.
It appears that this is still debatable in the field of endocrinology.
I'll try and find the foot noted articles later. I'd love to hear what some of the more knowledgeable members have to say about this.

[MuscleScience]

yeah I remember something about that on here. As far as what I have been taught in school is that it is down regulated.

[BG]

Interesting, I was always told that receptors regenerated consatantly and at a higher rate when test levels were higher just like estrogen. Hopefully some of the stronger minds will chime in on this. Good info to say the least. Was this school oriented? Nice to know an Endo.

[taiboxa]

i didnt take adderall today ><

[taiboxa]

I copied the quote and foot notes below from the following link.

http://forums.steroid.com/showthread.php?t=199833

Testosterone significantly increases the concentrations of the A. R in cells which are critical for muscle repair and growth.(4, 6 )

4 Curr Opin Clin Nutr Metab Care. 2004 May;7(3):271-7.
6 J Clin Endocrinol Metab. 2004 Oct;89(10):5245-55.

I'm not an endocrinologist but I thought that the idea of receptor down regulation or a decrease in receptor concentration while on cycle had been debunked a while ago.
It appears that this is still debatable in the field of endocrinology.
I'll try and find the foot noted articles later. I'd love to hear what some of the more knowledgeable members have to say about this.

yeah i bumped a REALLY good thread on this topic quite a while ago but its been about 6 months?

[MuscleScience]

Ok guys I went back through the lecture powerpt that he handed out because I was under the assumption that steroids pass right through the membrane of the cell since the are lipid soluble. Well as it turns out steroids pass through and bind to the AR receptor which is intra-cellular. Sorry for the in-accuracy. From what the powerpt says is that the actually AR receptors can change in it affinity for binding steroids after a prolonged exposure to high concentrations. It doesnt say in the notes that it changes concentration of AR receptors. I remember him saying something to the effect that it did. I guess I will be going through my physiology books looking for the answer. LOL

[MuscleScience]

. Was this school oriented? Nice to know an Endo.

I work in a molecular biology lab as well as a exercise physiology lab at my University were I received my masters. The guy two doors down is an Endo that researches cancer via the estradiol mechanism in breast and ovarian cancer. He was giving a lunch-time talk to faculty and students, as we have lectures like this weekly from different faculty and guest speaks. This is the only one I have gone to this year as its the only one that sounded interesting from the poster.

[jagdpanther]

AR receptors can change in it affinity for binding steroids after a prolonged exposure to high concentrations.

Is there an allosteric binding site on the AR that changes the teriatry conformation or something? I'm just really kind of interested in that level of detail. I'll look through some of my books as well -although being a long Monday I know Ihave a lot of boring resposibilities ahead of me beforeI can do any fun stuff.

[Pooks]

ok so it sounds like there are 3 parts at play here..

U got testosterone.
Than u got the AR enzyme
and than u have the receptors...

it appears the AR enyzme needs to attach itself to the Testosterone, and that is the only way its gonna be able to plug into the receptor.

I guess with steroid use...
the Receptors increase in numbers, because there needs to be more of them, to meet the demand..

but it appears that maybe the AR enzyme decreases in number,, making the steroid cycle less effective as it goes on.

now in the meantime your natural test production shuts down,
U go off the cycle...
the receptors are there..
but the AR enzyme, and the TEST levels are hurting.
and it will take time to bring them back up to par.

I suppose it would be beneficial to find a way to keep that AR enzyme at steady levels throughout the cycle.

not the 5-AR one = DHT one.. but just the AR one lol for the TEST

[MuscleScience]

Is there an allosteric binding site on the AR that changes the teriatry conformation or something? I'm just really kind of interested in that level of detail. I'll look through some of my books as well -although being a long Monday I know Ihave a lot of boring resposibilities ahead of me beforeI can do any fun stuff.

Basically, The AR receptor Enzyme attaches itself to the steroid molecule shuttling it into the nucleus of the cell. Were this enzyme/steroid complex binds directly to an area on the DNA molecule called a response element which then causes messenger RNA to leave the nucleus and direct ribosomes to produce proteins that further tell the cell what to do.

I could find wether the AR Enzyme was either allosteric or a covelant modulator.

[jagdpanther]

Basically, The AR receptor Enzyme attaches itself to the steroid molecule shuttling it into the nucleus of the cell. Were this enzyme/steroid complex binds directly to an area on the DNA molecule called a response element which then causes messenger RNA to leave the nucleus and direct ribosomes to produce proteins that further tell the cell what to do.

I could find wether the AR Enzyme was either allosteric or a covelant modulator.

Very cool bro!, thanks for the info.
I have a relativley modern biochem book that goes into a lot of detail but I haven't had a chance to sit down and go at. Hopefully after I do I'll have something toadd.

[MuscleScience]

Very cool bro!, thanks for the info.
I have a relativley modern biochem book that goes into a lot of detail but I haven't had a chance to sit down and go at. Hopefully after I do I'll have something toadd.

Yeah that would be great, My books and old physiology note basically generalize everything. Im going to do a more extensive primarly lit search later in the week so hopefully we can come up with some cool stuff.

MS

[kfrost06]

Very interesting thread discussion. I have often pondered this myself and though it's been a number of years since my BioChem days I do remember there is always a feedback mechanism for all the binding that goes on with receptors. I would imagine that when all your AR receptors are bound your body would respond by sending out Inhibitors(I) which can either bind to the receptor or the enzyme changing the configuration of either which then in turn decreases the Km(binding affinity), i.e. the lower the Km the stronger the binding of the enzyme to the receptor, the stronger the binding the more efficient. When all your recpetors are bound your body will try to "correct" it by first decreasing the production of whats binding, i.e. decrease test production. That will not work since it is being injected so inhibitors are produced to bind as mentioned before, decreasing the effectiveness. With my experience after awhile the test(et al) just stop working and if I do not take along enough break between cycles the next cycle does not work as good.

In addition to "getting your receptors back" when there is not enough binding going on your body will send out activators(A) that can make the binding stronger and increase the chances of binding. Your body is amazing when it comes to regulating itself. There is always feedback going on telling your body something is "out of the norm" and it will try to correct it. So, I assume this is going on with the ARs, the decrease in A and increases in I which will lower the effectiveness of any gear. I will see if I can do some research on this and add to this thread any info I can find.