urs
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look foidrapist6769the fact that u keep bringing up my username on a forum like its some kind of gotcha is peak deflection and honestly just shows uve run out of actual biological counterarguments to what im actually saying in this debate. its completely irrelevant to the mechanics of the endocrine system and growth plate physiology and the fact u even mention it shows ur grasping at straws because u cant actually refute the science behind what i'm presenting to u. Im trying to have a high level productive argument with u and thats it but u keep circling back to these basic points that dont even apply to the context of supra physiological rhgh usage and its getting repetitive at this point and quite frankly a waste of time. nothing im saying is contradicted by actual studies if u actually look at the underlying mechanics instead of just reading abstracts or taking surface level conclusions as gospel, much of it is directly supported by how signaling pathways work in chondrocytes, and the parts that dont have direct double blind human trials on 7 foot tall people (obviously because of ethics boards and the illegality of high dose gh for height enhancement) still have such strong mechanical links that they can be seen as proof to anyone who understands how gh and igf1 actually signal at the cellular level.
ur using studies on ghd or iss which almost always uses very insufficient dosages to even begin to mimic what actually happens in gigantism or what would happen with high dose exogenous use for performance or height and it shows a total lack of understanding of dose response curves. Both ISS and GHD studies shouldnt be perfectly used as a proxy for healthy people when it comes to taking exogenous rhgh for height because the baseline physiology is broken in those kids from the start and their receptors are often already downregulated or mutated. u cannot compare a kid with a genetic growth hormone receptor mutation or a literal pituitary deficiency to a healthy person with a functioning axis taking high doses of rhgh because the healthy person has a much higher ceiling for response. gigantism is a way better proxy because these people are often healthy and a normal height for a long time until the pituitary adenoma starts secreting massive amounts of gh and a lot of times that tumor has zero effect on any other pituitary axis so the whole "imbalance" argument u keep making is totally irrelevant and honestly just flat out wrong for most cases. I already sent that paper showing that in a very big amount of gigantism cases the gh secreting adenoma solely affects gh release and has 0 noticable effect on other hormones like lh fsh or tsh so stop bringing up broader pituitary disturbances like it changes anything because it doesnt change the fact that the height comes from gh and igf1 alone.
and since u mentioned children with normal endocrine function meaning ISS studies, these obviously cant be used for loads of reasons that u seem to be ignoring. they clearly have genetic traits limiting growth or directly affecting the ghr and its downstream effects which is why they are short in the first place despite "normal" levels of gh in their blood. like i showed u in that one case where some ISS patient had to receive 346mcg/kg/day of rhgh just to get into +2 SDS igf1 levels which is just the upper range of normal for their age group and is a massive dose that would make a normal person look like an ogre. if a healthy person with normal sensitivity took that much they would be at like 1500 igf1 and growing like a weed because they dont have the genetic bottleneck that the ISS kids have and their cells can actually process the signal. ur basically trying to use data from a broken car with a speed limiter to tell me how fast a race car can go if we give it better fuel it makes no sense and u know it but u keep pushing it because u have no other evidence.
I literally already debunked what u said about progenitor cells running out like three times now and u still keep saying it like its some gospel that cant be questioned. u dont need to have more progenitor cells to achieve more growth in the long run because gh/igf achieves it through multiple direct pathways like PI3K/Akt and MAPK/ERK which bypass the "natural" limits of the cell cycle. it increases the profileration rate as well as keeps them profilerating longer in the profilerative zone so it literally stretches out the time they spend dividing before they mature and eventually die off through programmed cell death. it also decreases apoptosis and increases hypertrophic cell size which means each individual cell contributes more to the actual length of the bone during the expansion phase in the growth plate. it also increases production of ecm components like collagen X and aggrecan and other proteoglycans in the hypertrophic zones which means the progenitor cells dont determine a hard ceiling on growth at all because the volume of the matrix itself expands under the influence of igf1. amount of chondrocyte cells and how much space the ecm takes up before the cells transdifferentiate or die and get converted to bone cells can all be changed after the resting zone and that part is highly respondent to factors like gh and igf1 which u can manipulate exogenously.
u also seem to ignore that the main driver of senescence and plate closure is estrogen signaling which is where aromatase inhibitors come in and change the game entirely for anyone trying to grow. if u use an AI u directly delay that senescence and keep the plates open way longer than they naturally would be by preventing the estrogen-mediated depletion of the resting zone progenitor pool. sure periods of extremely high gh and igf1 may speed up the velocity by a lot and maybe cause quicker senescence in a vacuum if u dont manage the other hormones but that doesnt mean that the growth cant outpace the closure. if u grow 5 inches in the time it would have normally taken to grow 1 inch even if the plates close slightly sooner ur still way ahead in final adult height and thats the only metric that matters. gigantism is literally the living proof of this and idk what u dont understand about it because its so clear. gigantism in a lot of cases is caused ONLY by the changes in gh release and if this works for height in those cases which it obviously does then it must also be true that injecting high amounts of rhgh exogenously to achieve the exact same blood concentrations and secretion patterns will produce the same effect aka a lot of height gains.
and no shit someone will get side effects doing this but thats up to the person if they want to risk it just like any other drug or compound they put in their body. im simply arguing that it works and that the "biological ceiling" u keep talking about is mostly a result of low gh levels and high estrogen signaling not some magical exhaustion of cells that cant be overcome with the right pharmacology. u claimed feedback mechanisms prevent this but they very easily dont and u havent provided any proof they do. the only 2 relevant feedback mechanisms are the hpg axis which we ignore because we use exogenous gh and the other one is the peripheral tissue feedback like socs proteins which are basically just intracellular brakes on the jack stat pathway. these arent valid arguments because they are just as present in gigantism as they would be with injections and the tumor doesnt affect those peripheral mechanisms at all. in gigantism they arent powerful enough to completely block the signal they only blunt it a bit and the massive gh levels just blast right through it. u also said gigantism leads to constant elevation which is easy to replicate by just splitting ur dose into 3 or 4 pins a day to keep it continuous or even using an insulin pump for gh which some people actually do. all ur arguments are debunked so stop circling back to the same points over and over even when they are irrelevant and have been proven wrong by anyone who understands endocrinology.
and u keep talking about the "resting zone" like its some static battery that just drains until it hits zero and then ur done. its not. its a dynamic reservoir and the rate of depletion is governed by paracrine and endocrine signals that we can influence. when u introduce supra-physiological gh ur not just draining the battery faster ur increasing the efficiency of every single cell that leaves that zone and enters the proliferative phase. the chondrocytes in the proliferative zone divide more times and the ones in the hypertrophic zone get larger before they undergo ossification into bone. so even if the resting zone eventually closes the total "height per cell" is vastly higher than it would be under natural conditions and that leads to more height. this is why giants reach 7 or 8 feet even if their plates close eventually—they simply extracted more longitudinal growth out of every single progenitor cell they had in their body. if what u said was true and the cells were the only limit then giants would grow at a normal rate but just for a much longer time like 40 years which isnt what happens in the real world. they grow faster and bigger simultaneously because the cellular machinery is being overclocked.
also u tried to say that exogenous gh doesnt mimic the pulsatility of natural gh but u can literally replicate that with modern administration protocols if u actually cared to look into it instead of just talking. but even then gigantism often involves a high baseline bleed of gh anyway which is exactly what happens with multiple daily injections of rhgh. the body doesn't care if the gh molecule came from a tumor in the brain or a needle in the fat it only cares about receptor occupancy and the downstream activation of igf1 in the liver and locally in the growth plates themselves. if the igf1 is elevated and the estrogen is suppressed by an AI there is literally nothing stopping the bone from extending further than its genetic "blueprint" intended because that blueprint is just a set of instructions based on average hormone levels. stop moving the goalposts and admit that the mechanical link between gh levels and longitudinal bone growth is the primary driver of height regardless of the source.
u keep acting like the growth plate is this fragile thing that just breaks if u push it but it is extremely robust and responsive to metabolic load. if u keep the inflammatory markers low and the nutrient density high while blasting gh the amount of bone u can lay down is insane. the whole idea that there is a fixed number of divisions a chondrocyte can go through is based on in vitro studies that dont account for the massive amount of growth factors present in a live human on 10iu of gh a day. when u change the environment u change the cell behavior. u cant use old textbooks to argue against modern results. plus u completely ignored my point about the ecm expansion which is like half of the height gain in the hypertrophic zone. even if the cells stopped dividing the expansion of the matrix alone would give u more height than a natural person. u have no answer for that because there is no answer that fits ur narrative. just admit u were wrong about the ceiling and we can move on to the actual application of this stuff instead of arguing about whether or not it works when the evidence is literally standing in front of u in the form of every giant in history.
ur using studies on ghd or iss which almost always uses very insufficient dosages to even begin to mimic what actually happens in gigantism or what would happen with high dose exogenous use for performance or height and it shows a total lack of understanding of dose response curves. Both ISS and GHD studies shouldnt be perfectly used as a proxy for healthy people when it comes to taking exogenous rhgh for height because the baseline physiology is broken in those kids from the start and their receptors are often already downregulated or mutated. u cannot compare a kid with a genetic growth hormone receptor mutation or a literal pituitary deficiency to a healthy person with a functioning axis taking high doses of rhgh because the healthy person has a much higher ceiling for response. gigantism is a way better proxy because these people are often healthy and a normal height for a long time until the pituitary adenoma starts secreting massive amounts of gh and a lot of times that tumor has zero effect on any other pituitary axis so the whole "imbalance" argument u keep making is totally irrelevant and honestly just flat out wrong for most cases. I already sent that paper showing that in a very big amount of gigantism cases the gh secreting adenoma solely affects gh release and has 0 noticable effect on other hormones like lh fsh or tsh so stop bringing up broader pituitary disturbances like it changes anything because it doesnt change the fact that the height comes from gh and igf1 alone.
and since u mentioned children with normal endocrine function meaning ISS studies, these obviously cant be used for loads of reasons that u seem to be ignoring. they clearly have genetic traits limiting growth or directly affecting the ghr and its downstream effects which is why they are short in the first place despite "normal" levels of gh in their blood. like i showed u in that one case where some ISS patient had to receive 346mcg/kg/day of rhgh just to get into +2 SDS igf1 levels which is just the upper range of normal for their age group and is a massive dose that would make a normal person look like an ogre. if a healthy person with normal sensitivity took that much they would be at like 1500 igf1 and growing like a weed because they dont have the genetic bottleneck that the ISS kids have and their cells can actually process the signal. ur basically trying to use data from a broken car with a speed limiter to tell me how fast a race car can go if we give it better fuel it makes no sense and u know it but u keep pushing it because u have no other evidence.
I literally already debunked what u said about progenitor cells running out like three times now and u still keep saying it like its some gospel that cant be questioned. u dont need to have more progenitor cells to achieve more growth in the long run because gh/igf achieves it through multiple direct pathways like PI3K/Akt and MAPK/ERK which bypass the "natural" limits of the cell cycle. it increases the profileration rate as well as keeps them profilerating longer in the profilerative zone so it literally stretches out the time they spend dividing before they mature and eventually die off through programmed cell death. it also decreases apoptosis and increases hypertrophic cell size which means each individual cell contributes more to the actual length of the bone during the expansion phase in the growth plate. it also increases production of ecm components like collagen X and aggrecan and other proteoglycans in the hypertrophic zones which means the progenitor cells dont determine a hard ceiling on growth at all because the volume of the matrix itself expands under the influence of igf1. amount of chondrocyte cells and how much space the ecm takes up before the cells transdifferentiate or die and get converted to bone cells can all be changed after the resting zone and that part is highly respondent to factors like gh and igf1 which u can manipulate exogenously.
u also seem to ignore that the main driver of senescence and plate closure is estrogen signaling which is where aromatase inhibitors come in and change the game entirely for anyone trying to grow. if u use an AI u directly delay that senescence and keep the plates open way longer than they naturally would be by preventing the estrogen-mediated depletion of the resting zone progenitor pool. sure periods of extremely high gh and igf1 may speed up the velocity by a lot and maybe cause quicker senescence in a vacuum if u dont manage the other hormones but that doesnt mean that the growth cant outpace the closure. if u grow 5 inches in the time it would have normally taken to grow 1 inch even if the plates close slightly sooner ur still way ahead in final adult height and thats the only metric that matters. gigantism is literally the living proof of this and idk what u dont understand about it because its so clear. gigantism in a lot of cases is caused ONLY by the changes in gh release and if this works for height in those cases which it obviously does then it must also be true that injecting high amounts of rhgh exogenously to achieve the exact same blood concentrations and secretion patterns will produce the same effect aka a lot of height gains.
and no shit someone will get side effects doing this but thats up to the person if they want to risk it just like any other drug or compound they put in their body. im simply arguing that it works and that the "biological ceiling" u keep talking about is mostly a result of low gh levels and high estrogen signaling not some magical exhaustion of cells that cant be overcome with the right pharmacology. u claimed feedback mechanisms prevent this but they very easily dont and u havent provided any proof they do. the only 2 relevant feedback mechanisms are the hpg axis which we ignore because we use exogenous gh and the other one is the peripheral tissue feedback like socs proteins which are basically just intracellular brakes on the jack stat pathway. these arent valid arguments because they are just as present in gigantism as they would be with injections and the tumor doesnt affect those peripheral mechanisms at all. in gigantism they arent powerful enough to completely block the signal they only blunt it a bit and the massive gh levels just blast right through it. u also said gigantism leads to constant elevation which is easy to replicate by just splitting ur dose into 3 or 4 pins a day to keep it continuous or even using an insulin pump for gh which some people actually do. all ur arguments are debunked so stop circling back to the same points over and over even when they are irrelevant and have been proven wrong by anyone who understands endocrinology.
and u keep talking about the "resting zone" like its some static battery that just drains until it hits zero and then ur done. its not. its a dynamic reservoir and the rate of depletion is governed by paracrine and endocrine signals that we can influence. when u introduce supra-physiological gh ur not just draining the battery faster ur increasing the efficiency of every single cell that leaves that zone and enters the proliferative phase. the chondrocytes in the proliferative zone divide more times and the ones in the hypertrophic zone get larger before they undergo ossification into bone. so even if the resting zone eventually closes the total "height per cell" is vastly higher than it would be under natural conditions and that leads to more height. this is why giants reach 7 or 8 feet even if their plates close eventually—they simply extracted more longitudinal growth out of every single progenitor cell they had in their body. if what u said was true and the cells were the only limit then giants would grow at a normal rate but just for a much longer time like 40 years which isnt what happens in the real world. they grow faster and bigger simultaneously because the cellular machinery is being overclocked.
also u tried to say that exogenous gh doesnt mimic the pulsatility of natural gh but u can literally replicate that with modern administration protocols if u actually cared to look into it instead of just talking. but even then gigantism often involves a high baseline bleed of gh anyway which is exactly what happens with multiple daily injections of rhgh. the body doesn't care if the gh molecule came from a tumor in the brain or a needle in the fat it only cares about receptor occupancy and the downstream activation of igf1 in the liver and locally in the growth plates themselves. if the igf1 is elevated and the estrogen is suppressed by an AI there is literally nothing stopping the bone from extending further than its genetic "blueprint" intended because that blueprint is just a set of instructions based on average hormone levels. stop moving the goalposts and admit that the mechanical link between gh levels and longitudinal bone growth is the primary driver of height regardless of the source.
u keep acting like the growth plate is this fragile thing that just breaks if u push it but it is extremely robust and responsive to metabolic load. if u keep the inflammatory markers low and the nutrient density high while blasting gh the amount of bone u can lay down is insane. the whole idea that there is a fixed number of divisions a chondrocyte can go through is based on in vitro studies that dont account for the massive amount of growth factors present in a live human on 10iu of gh a day. when u change the environment u change the cell behavior. u cant use old textbooks to argue against modern results. plus u completely ignored my point about the ecm expansion which is like half of the height gain in the hypertrophic zone. even if the cells stopped dividing the expansion of the matrix alone would give u more height than a natural person. u have no answer for that because there is no answer that fits ur narrative. just admit u were wrong about the ceiling and we can move on to the actual application of this stuff instead of arguing about whether or not it works when the evidence is literally standing in front of u in the form of every giant in history.
