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What are the degradation rates of GHRH receptors on pituitary somatotrophs?

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Posted on Sat, 16 May 2015
Question: Dear Dr. Saghafi,

you gave me some valued advice regarding various proteins in the brain and their degradation rates. I have further follow up questions:

I'm interested to know about degradation rates for Ghrh receptors on pituitary somatrophs. Furthermore, in case of 'recycling' how long before these are also degraded? Basically, are any ghrh receptors from my teen years present now in some recycled form? Any chance of this? Thanks and Best Regards
doctor
Answered by Dr. Dariush Saghafi (21 hours later)
Brief Answer:
Very interesting question without an easy answer

Detailed Answer:
I do believe I gave an approximate answer to you in my last response though it was not based on more than logic and extrapolation of facts that I took from knowing the dynamics of hormone degradation of hypothalamic products as well as the huge interplay between the hypothalamus and pituitary glands.

However, to find the EXACT number for the degradation rates for GHRH receptors in pituitary somatropes has been quite a daunting challenge. I have been reviewing the literature from many sources and I cannot find a number. Oddly enough, however, the GHRH receptor itself has a world of information known and published about it....I believe part of the problem in finding an exact number is that it really depends on a number of variables in an individual. GH itself is released on average every 3 hrs. into the circulation. But, this is dependent upon time of the day (mostly released at nighttime when the individual tends to be asleep), gender, and age. Obviously, the release of GH into the circulation of a 70 year individual is not the same amount nor frequency nor potency compared to a growing 15 year old.

However, there is (as I've previously stated) a clearcut supply/demand relationship so that even in a 70 year old...their other physiological activities having to do with things such as sexual activities, etc. may affect the rate and quantity of GH release which may be above the average for his age group. Therefore, in terms of the RECEPTORS for GHRH it is intuitively the case that one would expect either a greater active percentage of these receptors to be produced or a longer durability of the receptors depending upon how frequently they are being stimulated by circulating GHRH released by the hypothalamus.

For the purpose of passing at least this much information on to you I am sending the response and approximating once again receptor half life or turnover rate somewhere in the neighborhood of 3-3.3 hrs. in human beings. However, I would like to continue researching this very interesting question to see if I can't find something more specific on the kinetics of GHRHR's in the pituitary somatotropes...as I see you are already aware that GHRHR's also exist outside the pituitary/hypothalamic axis in places such as the heart and many other organs....

The query has required a total of 90 minutes of physician specific time to read, research, and compile a return envoy to the patient.


Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
doctor
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Follow up: Dr. Dariush Saghafi (3 hours later)
Thanks Dr Saghafi for the valued advice again.

Since your answers are the best, I would like your opinion on seprate topic - cardiac stem cells.

Apparently, anabolic steroids increase cardiac stem cell proliferation.

My concern is that these steroids i took, increased stem cell numbers, and these are still around today possibly in differentiated form (cardiac cells) and of course, we know cardiac cells are slow renewing. What would be your opinion on this?

Thanks and all my best
XXXXX

doctor
Answered by Dr. Dariush Saghafi (27 hours later)
Brief Answer:
Now we're traveling far outside my areas of expertise

Detailed Answer:
I am very happy to take a STAB at this question but must warn you that I am not expert or even NEAR expert in this information as it is well outside my realms of study as a neurologist. My interest in molecular biology and genetic control mechanisms over disease doesn't include this topic to any extent.

Still, what I know is that that cardiac fibroblasts are clearly affected into activity by estrogens as opposed to androgens. The overall effect is to cause a rapid stimulatory and proliferative effect on these stem cells.

Without knowing more about the steroids you took, the length of time you took them, and then, to know information about your heart itself in terms of its function (Ejection fraction, presence or not of hypertrophy of the ventricular muscles, etc.) I think it would be hard for ANYONE to answer your question with any certainty. Stem cells are not entities that are readily available to "counting" within a certain tissue or organ. I'm not even sure what the exact downside would be to stem cell proliferation in the heart IF IT EVEN OCCURRED.

I'm trying to imagine why this question would be of interest to you. Are you thinking that you have possibly generated pools of stem cells which if necessary could help you combat diseases such as congestive heart failure, or better recovery if you suffered an MI or something along those lines?

We also know that in terms of generalities estrogens have a cardioprotective effect and this clinical effect is seen in women by virtue of their suffering from heart disease much less than men do.

Again, the clinical implications of what all this means I believe is still being debated and is not crystal clear. I think it would be very difficult to quantify one way or the other that in your case there continue to be effects or remnants of the steroid exposure that you had some 18 years ago although if a proliferation of cardiac stem cells or fibroblasts did occur during the short period of time you were exposed I do not know what the longevity or such cell lines would be or how to utilize them to their maximum potential.

My thanks for having challenged me again with such an interesting question which I hope I've given you some additional information about but realize I wasn't quite able to hit the homerun I was hoping for given the fact, that it turned out to be in an area of slight deficiency on my part.

Nevertheless, this query required a total of 120 minutes of physician specific time to read, research, and compile a return envoy to the patient.


Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
doctor
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Follow up: Dr. Dariush Saghafi (14 hours later)
Dear Dr. Saghafi, I appreciate your indepth answers and advice.

I feel your indepth detailed answers can maybe help ease my dilemna.

My dilemna is the possibility of cardiac stem cell proliferation. The downside here is that it was caused by unnatural exogonous agents (anabolic steroid treatment) and not naturally. If these cell lines quickly turned over then i can move on. But if its long-lived then this would make me sad. Thats the reason i ask about turnover rates etc.

The problem is as follows: Exogonous steroid increased cardiac stem cell numbers, these stem cell differentiate into cardiac cells, and cardiac cells are slow turnover . So essentially the steroid has had a permanent impact in the form of newly proliferated stem cells .

If you can provide further valued opinions on this, i would be very grateful.

Thanks Dr. Saghafi, and all my best
doctor
Answered by Dr. Dariush Saghafi (27 hours later)
Brief Answer:
No evidence to support conjecture that stem cells HAVE actually matured

Detailed Answer:
Good morning. I understand your concern. I will try to shed some light from a purely CLINICAL PERSPECTIVE since I am not a molecular scientist by any means. So, while I agree that exposure to anabolic steroids has the potential to cause proliferation-- I am unaware of the clinical downsides to this type of event. For example, studies are available that demonstrate a relative protective effect of certain types of heart disease when cardiac tissue is exposed to estrogen. This is one possible explanation that some researchers have invoked to explain why women seem to have so much less cardiac disease than men (when correcting for habits of smoking, diabetes, hypertension, etc.). Some would say that the proliferation of stem cells is potentially a good thing since that increases the pool of "replacement" cells in case of emergency or damage.

So again, I'm not sure I would agree that just because you were exposed to anabolic steroids that automatically and unequivocally suggests that there should be a sequence of events that will or did unfold that will put at at risk for negative health situations in the future.

Secondly, I don't know that your statement "Exogenous steroid increased cardiac stem cell numbers....." is true because there is no feasible way of knowing how many stem cells you had 18 years ago in your heart, how many you had after exposure to the steroids, and how many you have today. You would literally have to take biopsies or specimens of the cardiac muscle and some how figure all of that out.....ain't gonna happen. Therefore, no way we can even prove the hypothesis that increased numbers of stem cells existed at that time or have persisted throughout time.

Thirdly, even if we assume that in fact, great numbers of stem cells arose from those steroid days some 18 years ago....can you point to any CLINICAL MANIFESTATIONS of importance that supports the notion that something bad has occurred as a direct consequence of having these increased numbers of stem cells? My guess is that you would be unable to show such cardiac events present that could be attributed either to increased numbers of stem cells....or increased numbers of stem cells that were pushed to differentiate into functional cardiac cells.

And the last statement: "So essentially the steroid has had a permanent impact in the form of newly proliferated stem cells."

Again, do you KNOW what the actual IMPACT has been on you of this stem cell proliferation or differentiation? I mean from a clinical point of view? The statement really cannot be proven and so the bottom line is; if it were me; and I'm only saying if it WERE ME in this situation I would not lose a second of sleep of whether or not I could possibly have increased stem cell numbers in my heart that could potentially become cardiac bound with some type of environmental pressure.

My vote is that you "move on" BECAUSE you realize that the conjectures are not provable to start. But even if we assume the initial hypotheses to be true in terms of there being a significant stem cell proliferation, if I had no direct clinical evidence of any negative impact that were going on in my body I would not be threatened by the presence of more cells.

Once again, many thanks for coming up with some interesting perspectives on molecular biology. I hope this last question has given you some information valid from a clinician's point of view and that you agree with me that under the circumstances my belief (until you tell me otherwise) is that you have quite a bit of longevity left in your cardiac muscle which you can protect and foment much more by eating healthily, not smoking, watching your weight, and exercising than by spending too much time worrying about downsides of a sequence of events which are neither easily provable nor related to any known clinical happenings of your over the past 18 years.

Since this is the final question in this series may I ask the favor of a SIMILAR HIGH STAR RATING on these last responses as well as a positive commentary which will allow this thread to be archived for further reference by colleagues as necessary.

This query required a total of 144 minutes of physician specific time to read, research, and compile a return envoy to the patient.

Live long and prosper!



Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
doctor
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Follow up: Dr. Dariush Saghafi (15 hours later)
Thanks Dr. Saghafi,

I know its now neccesarily negative to have more stem cells, but it means the steroids has left a lasting influence in the form of non-renewable cells (if the stem cells differentiated)

Any further opinion would be appreciated.

Thanks and all my best
doctor
Answered by Dr. Dariush Saghafi (2 hours later)
Brief Answer:
What is your PROOF that more stem cells are even present?

Detailed Answer:
I won't argue that point of view but again as a clinician and not a molecular biologist I must try again to convey to you to appreciate the point of view that you do not even have the proof to say with any certainty or authority that:

1. Increased #'s of stem cells in the heart (or anywhere else) directly as a consequence of this steroid exposure 18 years ago has even occurred......or do you?

2. Even if these stem cells had been produced or did come about as a result of steroid induced proliferation that there has been any CLINICAL MANIFESTATION they've exerted......again, or do you?


There is no way that I've been able to tell from the literature that such information can be known with the technology we have today. In other words the things that seem to be concerning to you (steroid induced proliferation of stem cells at the level of the heart as well as their maturation) are not things that could be proven by any laboratory or diagnostic means unless you literally take samples of the heart and do some type of assay for stem cell #'s. But as I said before, that's impossible to do in the live condition. You may be able to do it in a rat PERHAPS (and I'm not even convinced that's true) because you can sacrifice the animal, remove it's heart and do microscopic analysis for a survey of the types of cells present within the heart tissue and then, give an estimate of how many stem cells there are, etc. etc. etc.

You can't do that in a human.

My belief is that you're posing questions which cannot be answered but more importantly without the clinical data to support that any of what you think COULD'VE HAPPENED ACTUALLY DID....as a clinician I would say, "Don't Lose Sleep over this" Or, in your own words...."Move On...WITH CONFIDENCE"....

You Are Fine....just don't get into the situation that you were in 18 years ago with steroid exposure and you'll be grand!"

Make sense?

I couldn't even begin to CONJECTURE as to what you might be feeling as far as symptoms are concerned (though as far as you've said so far--- my guess is you feel fine in terms of your cardiac function, right) if you were to have increased cardiac myocytes which came from a line of "artificially induced stem cells" which proliferated on the basis of your being unwantedly exposed to these anabolic steroids. Make sense? I truly have not read anything in the literature after hours of scouring the Internet (Your questions really grabbed me as you can see! LOL) that addresses any of these points.

I just don't think anybody has done any of the experiments that you would need to have had done to be able to test your theories.....sooooooo....best thing to do is sit down as I'm doing right now...and enjoy....some Trader Joe's Popcorn with Herbs & Spices....this stuff is really incredible....I'm not kidding....you must get some if you've never had it....I can also guarantee that this popcorn will NOT change the # of stem cells anywhere in your body.....but it will make your taste buds stand up with joy! LOL....

May I ask you the favor at this point of CLOSING this QUERY by the completion of this response and simply rating my responses with a generous HIGH STAR RATING and written feedback so that it can be processed with the other end-of-the-month batch of work and archived for future reference for others to benefit from if necessary?

We can always pick up this discussion by your opening a new thread and I am happy to continue researching information and giving you my opinion so long as you keep in mind that we are well outside my expert levels of knowledge and experience when talking about CARDIAC MYOCYTES matured from STEM CELL LINEAGES induced by steroids 18 years ago! Hey-- where can I get me some of them? I might need a few extra spare tires in the trunk! HAHA!

SOUNDS LIKE A REAL WHO DUNNIT PLOT, DOESN'T IT? LOL!

Be well sir and see you in the next round of questions. Don't forget you can also specify that I answer your questions for you if you'd simply direct the query to my home page of: bit.ly/drdariushsaghafi

Cheers!

This query required a total of 174 minutes of physician specific time to read, (HEAVY DUTY) research, and compile a return envoy to the patient.


Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
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What are the degradation rates of GHRH receptors on pituitary somatotrophs?

Brief Answer: Very interesting question without an easy answer Detailed Answer: I do believe I gave an approximate answer to you in my last response though it was not based on more than logic and extrapolation of facts that I took from knowing the dynamics of hormone degradation of hypothalamic products as well as the huge interplay between the hypothalamus and pituitary glands. However, to find the EXACT number for the degradation rates for GHRH receptors in pituitary somatropes has been quite a daunting challenge. I have been reviewing the literature from many sources and I cannot find a number. Oddly enough, however, the GHRH receptor itself has a world of information known and published about it....I believe part of the problem in finding an exact number is that it really depends on a number of variables in an individual. GH itself is released on average every 3 hrs. into the circulation. But, this is dependent upon time of the day (mostly released at nighttime when the individual tends to be asleep), gender, and age. Obviously, the release of GH into the circulation of a 70 year individual is not the same amount nor frequency nor potency compared to a growing 15 year old. However, there is (as I've previously stated) a clearcut supply/demand relationship so that even in a 70 year old...their other physiological activities having to do with things such as sexual activities, etc. may affect the rate and quantity of GH release which may be above the average for his age group. Therefore, in terms of the RECEPTORS for GHRH it is intuitively the case that one would expect either a greater active percentage of these receptors to be produced or a longer durability of the receptors depending upon how frequently they are being stimulated by circulating GHRH released by the hypothalamus. For the purpose of passing at least this much information on to you I am sending the response and approximating once again receptor half life or turnover rate somewhere in the neighborhood of 3-3.3 hrs. in human beings. However, I would like to continue researching this very interesting question to see if I can't find something more specific on the kinetics of GHRHR's in the pituitary somatotropes...as I see you are already aware that GHRHR's also exist outside the pituitary/hypothalamic axis in places such as the heart and many other organs.... The query has required a total of 90 minutes of physician specific time to read, research, and compile a return envoy to the patient.