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How long do proteins in hypothalamus stay before being degraded and replaced by new proteins?

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Posted on Wed, 13 May 2015
Question: Dear Dr, im interested to know how long do proteins in hypothalamus neurons and dendrites stay before being degraded and replaced by new proteins ?

Thanks
doctor
Answered by Dr. Dariush Saghafi (9 hours later)
Brief Answer:
Multivariate analysis necessary to answer this question

Detailed Answer:
Good evening. My name is Dr. Saghafi and I am a neurologist from XXXXXXX OH. Your question is not directly answerable since there are a variety of considerations (variables if you will) that determine PROTEIN TURNOVER RATE in any part of the body which is a delicately balanced process of protein formation vs. degradation

This, in turn is a function mainly of body need for things such as hormones, neurotransmitters, structural proteins, etc. Also, another variable to consider which is nontrivial is the age of the organism. As can be expected the older the person the slower the turnover rate and calculation generally is for a particular protein under discussion.

There are also diurnal variations to consider meaning that depending upon what part of the day or night under discussion there is either an acceleration or slowing down of production of these entities which again, goes to overall need of the organism.

In the hypothalamus there have been some experiments looking at specific hormones and transmitters which are of importance.

As examples, dopamine and norepinephrine can be looked at in the hypothalamus. Measurements as well as calculations suggest that the following is true regarding to TURNOVER TIME:

1. DOPAMINE in the young individual and in the VENTROMEDIAL HYPOTHALAMUS is about 2.4 hrs. while in the middle aged individual is about 3.8 hrs.

2. NOREPINEPHRINE in the young individual and in the VENTROMEDIAL HYPOTHALAMUS is about 6.6 hrs. while in the middle aged individual is about 12.8 hrs.

You'll notice that not only are age and neurotransmitter type variables that determine different turnover times but even LOCATION within the hypothalamus is calculated differently.


Neuroendocrinology of Hormone-transmitter Interactions
edited by Hasan Parvez, XXXXXXX Parvez, XXXXXXX XXXXXXX
pp136-143, Vol. 1



In conclusion, there is not simply one answer for the question you ask but rather it must be specified which product of the hypothalamus you are interested in, the age of the individual, the overall health and nutritional status of the individual, and the location of where this product (neurotransmitter/hormone) is being manufactured as well as the time of day that the protein is being produced and/or utilized.

If this answer satisfactorily addresses your CHALLENGING question then, I'd appreciate the favor of a HIGH STAR RATING with some written feedback.

Also, CLOSING THE QUERY on your end (if there are no further comments) will be most helpful and appreciated so that this question can be transacted and archived for further reference by colleagues as necessary.

Please keep me informed as to the outcome of your situation by writing me at: bit.ly/drdariushsaghafi

All the best.

The query has required a total of 88 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)
Dear Dr. Saghafi,

Thank you for your indepth and valued answer. I really appreciate your time and help.

I'm interested in ghrh receptors at the site of pituitary somatropes. Reason being this possibly upregulated by the steroid treatment i took when i was 14.

I just wanna be sure these TREATMENT INDUCED receptors have long been replaced by new receptors.

I'm 32 now, is there any chance ghrh receptors from when i was 14 are still present now possibly in recycled form? Sorry if i've misunderstood the online articles.

Best Regards,
XXXX
doctor
Answered by Dr. Dariush Saghafi (21 hours later)
Brief Answer:
Pituitary GHRH receptors from age 14 LONG SINCE gone

Detailed Answer:
Thank you for your question. Depending upon the tissue or type of protein, its durability or turnover time can be protracted. For example, proteins that make up collagen fibers can last >70 years and there are certain proteins designed to last nearly 120 years!

However, in the pituitary gland the turnover times or durability of the manufactured proteins mimics the hypothalamus's situation. There is essentially a 1-1 correspondence between the hormones and proteins which act upon the pituitary. Therefore, the GHRH receptors which you believe were upregulated by steroids at age 14 are under no circumstance still viably functioning at the age of 32.

If this answer satisfactorily addresses your very INTERESTING question then, I'd appreciate the favor of a HIGH STAR RATING with some written feedback.

Also, CLOSING THE QUERY on your end (if there are no further comments) will be most helpful and appreciated so that this question can be transacted and archived for further reference by colleagues as necessary.

Please keep me informed as to the outcome of your situation by writing me at: bit.ly/drdariushsaghafi

All the best.

The query has required a total of 142 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 (2 hours later)
Thanks again Dr Saghafi,

what about the 'recycling' of ghrh receptors - i keep thinking that maybe some are still present now in recycled form. At what point can we say even the recycled receptors have degraded?

Or to put another way - when would the ENTIRE POOL of GHRH RECEPTORS AT 14 been COMPLETLEY DEGRADED (after recycling and re-recycling) and replaced by complete new pool?

I wouldl ike to close after this. Thanks and all the best
doctor
Answered by Dr. Dariush Saghafi (21 hours later)
Brief Answer:
Pool of GHRH RECEPTORS at age 14 seen recycling millions of times

Detailed Answer:
Are you familiar with the law related to the Conservation of Mass? It states that for any system closed to all transfers of matter and energy (both of which have mass), the mass of the system must remain constant over time, as system mass cannot change quantity if it is not added or removed.

Therefore, from a purely PHYSICAL POINT OF VIEW your GHRH receptors in fact, are clearly PRESENT in recycled form BUT they are NOT active receptors that function on the pituitary somatotropes anymore....but all the elements of those previously functioning receptors are certainly present within YOUR BODY...not the cell but YOUR BODY. But I will assume that's not exactly what you mean by recycled...correct?

The exact turnover rate, turnover or degradation time of the GHRHR or its complex with GHRH is a variable phenomenon as I've said in previous responses to this question. The exact kinetics with respect to the numbers you are seeking simply don't exist in generic form. One reason is because of what is referred to as a dimorphism of the receptor. There are at least 2 known pools of receptors which can be utilized by the pituitary somatotropes. One is a 40 amino acid sequence and the other is 44 amino acids. Both pools of receptors are plasma integrated proteins which means that like all plasma integrated receptors they are internalized by endocytosis, degraded by lysosomes and their elements sent back out (usually for reprocessing and reassembly). For most plasma based proteins and receptors this process occurs rapidly.

Remember, your question is about the RECEPTOR not any of the proteins that are manufactured by the cell due to second messenger pathways that occur when the hormone/receptor complex are formed (in this case GHRH/GHRHR).

Of all the resources I looked at the only one that gave any numbers with respect to this specific receptor found on pituitary somatotropes was by Brown et al in their published article A MODEL OF PITUITARY RELEASE OF GROWTH HORMONE which is an article found in the book:

Computation in Cellular and Molecular Biological Systems
By XXXXXXX Cuthbertson, Ray XXXXXXX
World Scientific Press, XXXXXXX 1, 1996
pp.329-338



I read the entire article with great interest. It is highly technical in its mathematical models and equations but the bottom line is that the releases of GROWTH HORMONE depending upon a myriad of factors which I've mentioned in other responses to your question goes anywhere from 30 minutes to 2.5 hrs.

This is very similar to what I had predicted earlier which was a life cycle for the receptors of 3-3.3 hrs. based upon circadian pulsed release of GH in the human condition.

Believe it or not the article makes significant mention of the CONSERVATION OF MASS ACTION which is not the same as CONSERVATION OF MASS, however, it does support a theory of what is referred to as receptor DESENSITIZATION and talks about how in this model other hormones such as somatostatin work to RESENSITIZE the receptor complex and the somatotrope in general to the effects of GHRH. However, resensitization does not necessarily mean that the SAME RECEPTOR complexes are being shut down and turned back on rather the entire POOL of receptors are being divided into a group which are variably sensitive as well as LESS SENSITIVE to the positive stimulation of GHRH (depending upon its concentration) and the mathematical formulae take into consideration that the entire pool of receptors are undergoing virtually a continuous flow of recycling or degradation but being reborn and then, sensitized by the ever present quantities of GHRH outside the cell.

The bottom line is this-- according to every resource I checked and rechecked there is no way that the same receptors that were present at age 14 can possibly be present at this time. They have been degraded, recycled, and rehabilitated or recapacitated millions if not billions of time since you were exposed to steroids.

I hope that this answer satisfactorily addresses your question which really pushes us to the limits of what is currently known as to the kinetics and molecular dynamics of plasma receptors of the GHRH family. If so, I'd appreciate the favor of a HIGH STAR RATING with some written feedback.

Also, CLOSING THE QUERY on your end will be most helpful and appreciated so that this question can be transacted and archived for further reference by colleagues as necessary. If I run into any other information I will include it in my response to the other pending question that I am still answering for you through the other question.

Clearly, I will have to admit that these series of questions have been some of the most challenging basic science and molecular chemistry questions I've had to research in a very long time. I hope it was as interesting for you to read (and I hope I kept the reading interest level appropriate for you even though I know you were looking for very specific number) as it was for me to research and cross reference multiple sources to try and Sherlock Holmes things together since there simply are no numbers of the type you seek.

Please keep me informed as to the outcome of your situation by writing me at: bit.ly/drdariushsaghafi

All the best.

The query has required a total of 214 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
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Dr. Dariush Saghafi

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How long do proteins in hypothalamus stay before being degraded and replaced by new proteins?

Brief Answer: Multivariate analysis necessary to answer this question Detailed Answer: Good evening. My name is Dr. Saghafi and I am a neurologist from XXXXXXX OH. Your question is not directly answerable since there are a variety of considerations (variables if you will) that determine PROTEIN TURNOVER RATE in any part of the body which is a delicately balanced process of protein formation vs. degradation This, in turn is a function mainly of body need for things such as hormones, neurotransmitters, structural proteins, etc. Also, another variable to consider which is nontrivial is the age of the organism. As can be expected the older the person the slower the turnover rate and calculation generally is for a particular protein under discussion. There are also diurnal variations to consider meaning that depending upon what part of the day or night under discussion there is either an acceleration or slowing down of production of these entities which again, goes to overall need of the organism. In the hypothalamus there have been some experiments looking at specific hormones and transmitters which are of importance. As examples, dopamine and norepinephrine can be looked at in the hypothalamus. Measurements as well as calculations suggest that the following is true regarding to TURNOVER TIME: 1. DOPAMINE in the young individual and in the VENTROMEDIAL HYPOTHALAMUS is about 2.4 hrs. while in the middle aged individual is about 3.8 hrs. 2. NOREPINEPHRINE in the young individual and in the VENTROMEDIAL HYPOTHALAMUS is about 6.6 hrs. while in the middle aged individual is about 12.8 hrs. You'll notice that not only are age and neurotransmitter type variables that determine different turnover times but even LOCATION within the hypothalamus is calculated differently. Neuroendocrinology of Hormone-transmitter Interactions edited by Hasan Parvez, XXXXXXX Parvez, XXXXXXX XXXXXXX pp136-143, Vol. 1 In conclusion, there is not simply one answer for the question you ask but rather it must be specified which product of the hypothalamus you are interested in, the age of the individual, the overall health and nutritional status of the individual, and the location of where this product (neurotransmitter/hormone) is being manufactured as well as the time of day that the protein is being produced and/or utilized. If this answer satisfactorily addresses your CHALLENGING question then, I'd appreciate the favor of a HIGH STAR RATING with some written feedback. Also, CLOSING THE QUERY on your end (if there are no further comments) will be most helpful and appreciated so that this question can be transacted and archived for further reference by colleagues as necessary. Please keep me informed as to the outcome of your situation by writing me at: bit.ly/drdariushsaghafi All the best. The query has required a total of 88 minutes of physician specific time to read, research, and compile a return envoy to the patient.