Something that is often forgotten by people who are trying to stimulate the pituitary gland to release excess human growth hormone for height increase and to grow taller is that the pituitary gland is not the actual real originator of the hormone pathway. It is the hypothalamus which controls how much somatotropin will be allowed to be released by the pituitary gland.

From source, we find out what are the types of hormones the hypothalamus will released…

The hypothalamus is a region of the brain . It contains several types of neurons responsible for secreting different hormones.

• Thyrotropin-releasing hormone (TRH)
• Gonadotropin-releasing hormone (GnRH)
• Growth hormone-releasing hormone (GHRH)
• Corticotropin-releasing hormone (CRH)
• Somatostatin
• Dopamine

All of these are released into the blood in the capillaries and travel immediately – in portal veins – to a second capillary bed in the anterior lobe of the pituitary, where they exert their effects.

All of them are released in periodic spurts. In fact, replacement hormone therapy with these hormones does not work unless the replacements are also given in spurts.

Two other hypothalamic hormones are vasopressin and oxytocin which travel in the neurons themselves to the posterior lobe of the pituitary where they are released into the circulation.

It would go slightly more detailed on the effects of the Growth hormone-releasing hormone (GHRH)..

Growth Hormone-releasing Hormone (GHRH): GHRH is a mixture of two peptides, one containing 40 amino acids, the other 44. As its name indicates, GHRH stimulates cells in the anterior lobe of the pituitary to secrete growth hormone (GH).

There is also the fact that the hypothalamus will be releasing another hormone which will have an ibhibitory effect on the pituitaty gland in regulating the excess release of growth hormone.

Somatostatin: Somatostatin is a mixture of two peptides, one of 14 amino acids, the other of 28. Somatostatin acts on the anterior lobe of the pituitary to…

• inhibit the release of growth hormone (GH)
• inhibit the release of thyroid-stimulating hormone (TSH)

Somatostatin is also secreted by cells in the pancreas and in the intestine where it inhibits the secretion of a variety of other hormones.

Now, there are at least 8 of these hormones the hypothalamus will be in control of regulating. We will only focus on the Somatostatin and the Growth Hormone-releasing Hormone because they are most relevant to any possible ideas on figuring out how to induce or increase longitudinal growth.

Things like gonadotropin releasing hormone, dopamine, vasopressin, and oxytocin are related to the onset bodily signs of puberty and the regulation of moods and emotions, at least from what we remember from those commercials on TV. As for thyrotropin-releasing hormone and corticotropin-releasing hormone I know every little except that the corticotropin-releasing hormone is released as a response to stress and that corticosteroids are increased.

In our past posts that we had spend a little bit of time looking at the pathways and mechanisms on how the pituitary gland affects the other glands in the endocrine system like the adrenal glands.

From the Wikipedia article on Growth Hormone-releasing Hormone, 

Growth-hormone-releasing hormone (GHRH), also known as growth-hormone-releasing factor (GRF, GHRF), somatoliberin or somatocrinin, is a releasing hormone for growth hormone. It is a 44 – amino acid peptide hormone produced in the arcuate nucleus of the hypothalamus.

GHRH is released from neurosecretory nerve terminals of these arcuate neurons, and is carried by the hypothalamo-hypophyseal portal system to the anterior pituitary gland where it stimulates growth hormone (GH) secretion by stimulating the growth hormone-releasing hormone receptor. GHRH is released in a pulsatile manner, stimulating similar pulsatile release of GH. In addition, GHRH also promotes slow-wave sleep directly. Growth hormone is required for normal postnatal growth, bone growth, regulatory effects on protein, carbohydrate, and lipid metabolism.

Effect

GHRH stimulates GH production and release by binding to the GHRH Receptor (GHRHR) on cells in the anterior pituitary.

Analysis & Interpretation:

We can say that the growth hormone releasing hormone seems to be pulsing at a similar rate as the growth hormone itself. What I wonder is whether stimulation of the hypothalamus indirectly will be able to cause excess release of the growth hormone releasing hormone but be able to inhibit the release of somatostatin.

Note: We have already gone over this diagram and well known process many times before in previous posts in the website.

If we can be able to just promote the release of GHRH and prevent also the release of Somatostatin the GH from the pulsating anterior region of the pituitary gland should be able to cause IGF-1 production from the live and also directly effect the growth plates of still developing individuals.

Nature has many ways to prevent organisms from growing out of control so we can see that there is at least two negative feedback loops in the diagram to keep the human body from growing to a crazy size. The IGF-1 produced goes back to increase the amount of somatostatin release by both the hypothalamus and the pituitary gland regions.

If this diagram is a true completed representation of the major routes to possibly increase height in the human body, then we can say that we can block the negative feedback loop process. At this point it could be as simple as putting a filter in the blood vessels that are veins which lead back into the heart and the brain. If we can keep the large sized proteins out of the blood stream then there would not be a signal telling the hypothalamic-pituitary region to stop.

However we did learn that both the GH and the IGF-1 can locally affect the growth plates from a subcetanous incision or injection. The easiest method that physicians have done to promote the increased longitudinal growth of children who have growth hormone defiency is to inject synthetic types of human growth hormone into their arm or shoulder. What I propose that can be simpler is to instead inject IGF-1 and synthetic hGH extremely close to the region of the growth plates. Sure, the old way of injecting so that the hormone will flow throughout the blood and effect all the areas of the body will lead to proportional growth, but if we are focused only on trying to increase our height, it would be smarter then to focus the injections of IGF-1 directly to the growth plate region to gain a higher level of effect. This will be a way to show how we can get around the negative feedback loop of the GHRH/HGH/IGF-1 interactions.

Me: Mecasermin is a type of synthetic IGF-1 that is made to be used in growth hormone therapy for people who have a stunted growth from IGF-1 deficiency. It acts and serves in the same way as somatropin use in growth hormone therapy. It’s branded and sold commercially as Increlex. It is FDA approved and can only be obtained from a doctor’s prescription.

As always this drug is to be used for young children who are still possibly growing. It is not intend to be used for people who have already reached physical maturity.

From the wikipedia article on it (source HERE)…

Mecasermin (INN, brand name Increlex) is recombinant human insulin-like growth factor 1 (IGF-I) which is used for the long-term treatment of growth failure in children with severe primary IGF-I deficiency.^[1][2]

This drug is not to be confused with mecasermin rinfabate (trade name: Iplex), which is the binary complex of recombinant human IGF-1 (rhIGF-1) and the binding protein that IGF-1 is naturally adhered to in the human body.

From the main Increlex website (source HERE)…

How Does Increlex^® Work?

Learn about what interrupts normal growth.
Click Here

Increlex is a liquid that contains man-made insulin-like growth factor (IGF-1), which is the same as the IGF-1 made by your body. Increlex, the only FDA-approved treatment for severe Primary IGFD, works by replacing the IGF-1, that your child’s body is lacking. It is different than growth hormone therapy. Children with severe Primary IGFD already produce enough growth hormone—what they need is replacement of IGF-1 specifically. How does Increlex go about replacing IGF-1?

• IGF-1 is injected under the skin and enters the bloodstream
• Some IGF-1 binds with carrier proteins, which move it throughout the blood vessels
• IGF-1 then arrives at growth plates, which are located near the ends of bones
• When IGF-1 arrives at the growth plate, bone cells divide, resulting in growth

Indication and Important Safety Information

Who is Increlex^® for?
INCRELEX is used to treat children who are very short for their age because their bodies do not make enough IGF-1. This condition is called severe primary IGF-1 deficiency. INCRELEX should not be used instead of growth hormone.

Who should not use Increlex?
Your child should not take INCRELEX if your child: has finished growing (the growth plates at the end of the bones are closed); has cancer; has other causes of growth failure; OR is allergic to mecasermin or any of the inactive ingredients in INCRELEX. INCRELEX has not been studied in children under 2 years of age and should never be used in newborns. Your child should never receive INCRELEX through a vein.

IGF-1 Is an Important Factor in the Growth of Children

The Difference between IGF-1 and Growth Hormone

Learn about what interrupts normal growth.
Click Here

Low levels of hormones, or body messengers, cause some short stature disorders. There are a number of critical hormones that are responsible for growth in children. Two of the most important are growth hormone and IGF-1. The first, growth hormone, is produced in the pituitary gland, which is a pea-sized gland located at the base of the brain. Growth hormone travels throughout the body. When it reaches the liver, it binds to receptors on liver cells, stimulating the liver to make a second hormone, insulin-like growth factor, or IGF-1.

IGF-1 is a critical factor in the growth of children.

The binding of IGF-1 to its receptors is responsible for the following changes in the body⁵:

• Increased protein synthesis
• Cell growth
• Increased cartilage formation and growth
• Skeletal growth

So, even if a child has normal levels of growth hormone, he or she still may not be growing properly. In particular, for children with severe Primary IGFD, exceptionally low levels of IGF-1 may be responsible. Children with normal growth hormone levels and exceptionally low IGF-1 levels may have a condition called severe Primary Insulin-like Growth Factor Deficiency, or severe Primary IGFD.

What does this mean for parents? Above all, it means that children who are tested for short stature disorders should be given a blood test that screens for severe Primary IGFD. The two results together will provide their physician with a more complete picture from which to make a more accurate diagnosis.

What to Know about Injecting Increlex^®

Overcoming Injection Anxiety

Because Increlex involves twice-daily injections, your child may be anxious about getting them, which can make you anxious, too. Fortunately, there are ways you can reduce this anxiety:

Develop a routine. Give Increlex injections around the same time each day, and choose a quiet and calm place, separate from where your child plays and eats, and away from the hustle and bustle of the house. Because Increlex is injected in the morning and evening, your child doesn’t have to worry about needing injections while at school. This should ease fears he might have about other kids finding out.

Relax. Create a soothing atmosphere. Play your child’s favorite music or videos as a distraction, or tell stories and jokes to distract him. Also teach your child breathing techniques, which can help to calm the emotions your child may be feeling.

Engage in positive thinking. Work with your child to think of ways he can mentally “escape” during the injection. Have your child practice visualizing a place or activity that makes him happy and concentrating hard on that mental picture instead of on the shot.

Choose timing wisely. Try to schedule the injection immediately before an activity that your child really enjoys, such as bath time or a favorite TV show. That way, your child can look ahead to the treat instead of focusing on the injection. Also, be sure your child eats shortly before or shortly after getting his injection. This will help to avoid hypoglycemia (low blood sugar).

Project the right attitude. Be careful that you don’t contribute to anxiety by making a big deal out of the injection. Don’t be dramatic, apologetic or overly sympathetic about it. Remain matter-of-fact and business-like during the few minutes you spend giving the injection, and then always give your child a big hug and words of praise afterward.

Talk it out. It is helpful to pick a time when you’re not giving injections to talk with your child about his anxiety. What goes through your child’s mind when it’s time to get the shot? Are there particular words or phrases your child tends to think about when feeling anxious? Try to come up with a sort of mantra—a positive and helpful phrase or sentence your child can repeat to himself whenever anxious thoughts start to creep in.

At some point in my research, I realized that one critical pathway I had to familiarize myself with was a signaling pathway called the AKT signaling pathway. This post is my attempt at understanding it and how it is related to human growth. One thing to note is that it seems the AKT pathway is also named the PI3K pathway but the PI3K is different from the AKT although the two parts are connected..

It turns out that this pathway is quite complex. A simpler way for the reader is just to watch this YouTube video HERE.

Note: A Lot of the information and material I will write up below will be also be transferred and added to the section for “Protein/Hormone Pathway Map” post/section as well as the “Molecular Biology, Biochemistry” section. As always, any section and sub-section of the website will always be edited and added upon as time goes on. 

From source 1, it seems that “PI3K activation activates AKT which activates mTOR.” As we remember mTOR has been shown to be involved in possible height increase since its inhibitor rapamycin also destroys leucine which is shown to play a role in growth.

From source 2, I post a picture of the mTOR/AKT/PI3K pathway below. For this diagram, the arrows seem to mean either you are inhibiting something or promoting it.

The two major parts of the pathway is are the PI3Ks and the AKTs

The type of pathway shows what happens from the cell’s cytoplasm to the cell’s nucleus. In the nucleus you have three types of information transformation, transcription, reverse transcription, and translation.

From the Wikipedia article on mTOR inhibitors…

The mammalian target of rapamycin (mTOR) also known as mechanistic target of rapamycin or FK506 binding protein 12-rapamycin associated protein 1 (FRAP1) is a protein which in humans is encoded by the FRAP1 gene.

Function

mTOR is a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription. mTOR belongs to the phosphatidylinositol 3-kinase-related kinase protein family.

mTOR integrates the input from upstream pathways, including insulin, growth factors (such as IGF-1 and IGF-2), and amino acids. mTOR also senses cellular nutrient and energy levels and redox status. The mTOR pathway is dysregulated in human diseases, especially certain cancers, Rapamycin is a bacterial product that can inhibit mTOR by associating with its intracellular receptor FKBP12. The FKBP12 rapamycin complex binds directly to the FKBP12-Rapamycin Binding (FRB) domain of mTOR.

mTOR is the catalytic subunit of two molecular complexes.

mTOR stands for mammalian Target Of Rapamycin and was named based on the precedent that TOR was first discovered via genetic and molecular studies of rapamycin-resistant mutants of Saccharomyces cerevisiae that identified FKBP12, Tor1, and Tor2 as the targets of rapamycin and provided robust support that the FKBP12-rapamycin complex binds to and inhibits the cellular functions of Tor1 and Tor2.

Analysis & Interpretation:

It would seem that the PI3K/AKT/mTOR pathway is one of the most important pathways in the intracellular system (within the cytoplasm). The mTOR is the target protein (mammalian target and mechanistic target) of something else called a Rapamycin. The other name for this protein is FK506 binding protein 12-rapamycin associated protein 1 (FRAP1). mTOR has the big job of regulating growth, cell proliferation, survical, protein synthesis, and transcription. The thing is that when the IGF-1, IGF-2, insulin which are growth factors come to the body, they are combined together by this protein. This shows that it is a sort of a middle of the process and critical element determining the effectiveness of the growth factors we get in our bodies. It also has the ability to sense cell nutrient and energy levels. When there is a type of diseases, the pathway’s ability to regulate stuff gets disrupted like in cancer. The way that rapamycin blocks the mTOR is to get itself attached to the mTOR receptor, something called FKBP12. When the FKBP12 is connected the the rapamycin, the complex that is formed inhibits the function of Tor1 and Tor2.

From the Wikipedia article on the Serine/Threonine Protein Kinase ,

A serine/threonine protein kinase is a kinase enzyme that phosphorylates the OH group of serine or threonine (which have similar sidechains). At least 125 of the 500+ human protein kinases are serine/threonine kinases (STK)….Serine/Threonine Kinase receptors plays a role in the regulation of cell proliferation, programmed cell death (apoptosis), cell differentiation, and embryonic development.

Analysis & Interpretation:

What we learn about a serine and/or threonine protein kinase is that it is a type of enzyme that takes off the -OH ends of the serine and threonine amino acids and replaces the stub where the -OH group used to be with a phosphate group, a PO4(3-). It seems that there is a bigger group known as protein kinases. Within this bigger group of protein kinases, the serine/threonine kinases are the subset but represent a huge percentage of the number of protein kinases in the human body. We learn that the receptors for the serine and threonine protein kinases have some sort of role in the regulation of cell proliferation, in apoptosis, cell differentiation, and embryonic development. It is very clear from this small section that the serine/threonine protein kinases as a group is very important in determining the growth and development of the cells and the human body. Since the mTOR is a type of protein kinase, it would be important as well.

From the Wikipedia article on Kinase…

In biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases. Kinases are not to be confused with phosphorylases, which carry out phosphorolysis, the breaking of a bond using an inorganic phosphate group; or with phosphatases, which remove phosphate groups.

Types

One of the largest groups of kinases are protein kinases, which act on and modify the activity of specific proteins. Kinases are used extensively to transmit signals and control complex processes in cells. More than five hundred different kinases have been identified in humans. Their enormous diversity, as well as their role in signaling, makes them an object of study.

Various other kinases act on small molecules such as lipids, carbohydrates, amino acids, and nucleotides, either for signaling or to prime them for metabolic pathways. Kinases are often named after their substrates.

Analysis & Interpretation:

We get another definition of what the term “phosphorylation” actually means. Phosphorylation is where a molecule in a state of high energy donates (transfers) a phosphate group (PO4(3-)) to a specific substrate. An example of a high energy donor molecule would be ATP (Adenosine triphosphate). Protein Kinases specfically change the activity of specific proteins. Kinases in general are used a lot to transmit signals and complex processes in cells.

From the Wikipedia article on Protein Kinase…

A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them (phosphorylation). Phosphorylation usually results in a functional change of the target protein (substrate) by changing enzyme activity, cellular location, or association with other proteins. The human genome contains about 500 protein kinase genes and they constitute about 2% of all human genes. Protein kinases are also found in bacteria and plants. Up to 30% of all human proteins may be modified by kinase activity, and kinases are known to regulate the majority of cellular pathways, especially those involved in signal transduction.

The chemical activity of a kinase involves transferring a phosphate group from a nucleoside triphosphate (usually ATP) and covalently attaching it to specific amino acidswith a free hydroxyl group. Most kinases act on both serine and threonine (serine/threonine kinases), others act on tyrosine (tyrosine kinases), and a number act on all three (dual-specificity kinases). There are also protein kinases that phosphorylate other amino acids, including histidine kinases that phosphorylate histidine residues.

Regulation

Because protein kinases have profound effects on a cell, their activity is highly regulated. Kinases are turned on or off by phosphorylation (sometimes by the kinase itself – cis-phosphorylation/autophosphorylation), by binding of activator proteins or inhibitor proteins, or small molecules, or by controlling their location in the cell relative to their substrates.

Analysis & Interpretation:

Protein kinase is an enzyme (aka protein which chances the function of other proteins by adding a molecular unit of a phosphate group to them. This process of adding a phosphate group is called phosphorylation. The protein that gets a phosphate group added on is known as the target protein as well as the substrate. Their activity, location, and way they interact with other proteins all get changed. There is around 500 protein kinases and they make up around 2% of the all the genes in the genome. About 30% of all human proteins can be changed by the function of the kinases. One of the functions of the kinases is to regulate the pathways in the cells, but most especially the ones that are involved in sinal transduction.

From the website CellSignal.com, I post a picture below that I found from the website.

Pathway Description:

Since its initial discovery as a proto-oncogene, the serine/threonine kinase Akt (also known as protein kinase B or PKB) has become a major focus of attention because of its critical regulatory role in diverse cellular processes, including cancer progression and insulin metabolism. The Akt cascade is activated by receptor tyrosine kinases, integrins, B and T cell receptors, cytokine receptors, G protein coupled receptors and other stimuli that induce the production of phosphatidylinositol 3,4,5 triphosphates (PtdIns(3,4,5)P3) by phosphoinositide 3-kinase (PI3K). These lipids serve as plasma membrane docking sites for proteins that harbor pleckstrin-homology (PH) domains, including Akt and its upstream activator PDK1. There are three highly related isoforms of Akt (Akt1, Akt2, and Akt3) and these represent the major signaling arm of PI3K. For example, Akt is important for insulin signaling and glucose metabolism, with genetic studies in mice revealing a central role for Akt2 in these processes. Akt regulates cell growth through its effects on the mTOR and p70 S6 kinase pathways, as well as cell cycle and cell proliferation through its direct action on the CDK inhibitors p21 and p27, and its indirect effect on the levels of cyclin D1 and p53. Akt is a major mediator of cell survival through direct inhibition of pro-apoptotic signals such as Bad and the Forkhead family of transcription factors. T lymphocyte trafficking to lymphoid tissues is controlled by the expression of adhesion factors downstream of Akt. In addition, Akt has been shown to regulate proteins involved in neuronal function including GABA receptor, ataxin-1, and huntingtin proteins. Akt has been demonstrated to interact with Smad molecules to regulate TGFβ signaling. Finally, lamin A phosphorylation by Akt could play a role in the structural organization of nuclear proteins. These findings make Akt/PKB an important therapeutic target for the treatment of cancer, diabetes, laminopathies, stroke and neurodegenerative disease.

As for the AKT in the pathway, it seems that like the mTOR, it is also another serine/threonine protein kinase. From the Wikipedia article on AKT…

Akt, also known as Protein Kinase B (PKB), is a serine/threonine-specific protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration.

Function

Akt regulates cellular survival and metabolism by binding and regulating many downstream effectors, e.g. Nuclear Factor-κB, Bcl-2 family proteins and murine double minute 2 (MDM2).

Cell survival: Overview of signal transduction pathways involved in apoptosis.

Akt could promote growth factor-mediated cell survival both directly and indirectly. BAD is a pro-apoptotic protein of the Bcl-2 family. Akt could phosphorylate BAD on Ser136,^[13] which makes BAD dissociate from the Bcl-2/Bcl-X complex and lose the pro-apoptotic function. Akt could also activate NF-κB via regulating IκB kinase(IKK), thus result in transcription of pro-survival genes.

Cell Cycle: Akt is known to play a role in the cell cycle. Under various circumstances, activation of Akt was shown to overcome cell cycle arrest in G1 and G2 phases. Moreover, activated Akt may enable proliferation and survival of cells that have sustained a potentially mutagenic impact and, therefore, may contribute to acquisition of mutations in other genes.

The PI3K stands for the term “Phosphatidylinositide 3-kinases (PI 3-kinases or PI3Ks)”. From the Wikipedia article on the PI3K…

“….are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. PI3Ks are a family of related intracellular signal transducer enzymes capable of phosphorylating the 3 position hydroxyl group of the inositol ring of phosphatidylinositol (PtdIns). They are also known as phosphatidylinositol-3-kinases. The pathway, with oncogene PIK3CA and tumor suppressor PTEN (gene), is implicated in insensitivity of cancer tumors to insulin and IGF1, in calorie restriction.

Function

PI 3-kinases have been linked to an extraordinarily diverse group of cellular functions, including cell growth, proliferation, differentiation, motility, survival and intracellular trafficking. Many of these functions relate to the ability of class I PI 3-kinases to activate protein kinase B (PKB, aka Akt) as in the PI3K/AKT/mTORpathway. The p110δ and p110γ isoforms regulate different aspects of immune responses. PI 3-kinases are also a key component of the insulin signaling pathway.”

Conclusion:

At this point, the spiderweb on how each protein or enzyme or kinase interact with each other is super complicated. I do understand that the arrows tell you whether the beginning component will either inhibit or promote the second component. From the diagram below here, we can make a very general outline on how the PI3K/AKT/mTOR Signaling pathway works without going into the big details to keep things simple, at least for right now. You have a growth factor (like insulin, IGF-1 or IGF-2) coming in to reach past the membrane that surrounds each cells that holds the cytoplasm inside. It has to pass through the bi-lipid layer. Once it gets past the layer, it will get into the cell and this is where the intracellular pathway will happen. Somehow a p110 and p85 is trigger, which will result in the triggering of something known as PIP2 allong with them to create or promote PIP3. This leads to the AKT kinase being trigger. That triggers the mTOR kinase. Eventually all of the cascading pathway has a result on the way the nucleus DNA does its translating, transcription, gene expression, and protein synthesis. It is clear from the number of interactions, lines, and arrows that each of the major elements in this pathway has multiple (and I mean MULTIPLE) roles and functions in the development, growth, proliferation, and differentiation of cells.

Laron Syndrome is another type of dwarfism that comes about from the lack of ability of the growth hormone receptors. What seems to be a good thing is that with the short stature, there is less chance for diabetes or cancer.

From the wikipedia article on Laron Syndrome HERE…

Laron syndrome, or Laron-type dwarfism, is an autosomal recessive disorder characterized by an insensitivity to growth hormone (GH), caused by a variant of thegrowth hormone receptor. It causes short stature and a resistance to diabetes and cancer.

It is named after Zvi Laron, the Israeli researcher who, with A. Pertzelan and S. Mannheimer, first reported the condition in 1966,^[1][2] based upon observations which began in 1958.^[3]Eponym

Resistance to GH was first reported by Laron in 1966. Since then, severe resistance to GH, characterized by grossly impaired growth despite normal levels of GH inserum, has been termed Laron syndrome.

Pathophysiology

Laron syndrome has an autosomal recessive pattern of inheritance.

Molecular genetic investigations have shown that this disorder is mainly associated with mutations in the gene for the GH receptor. These can result in defectivehormone binding to the ectodomain or reduced efficiency of dimerization of the receptor after hormone occupancy. There are exceptionally low levels of insulin-like growth factor (IGF-1) and its principal carrier protein, insulin-like growth factor binding protein 3.

A related condition involving postreceptor insensitivity to growth hormone has been associated with STAT5B.^[4]

Clinical characteristics

The principal feature of Laron syndrome is abnormally short stature (dwarfism). Physical symptoms include: prominent forehead, depressed nasal bridge, underdevelopment of mandible, truncal obesity^[5] and a very small penis. Seizures are frequently seen secondary to hypoglycemia. Some genetic variations have an impact upon intellectual capacity.^[6]

The majority of reported cases have been of Arabic or Semitic origin, with numerous patients in Israel, Saudi Arabia, Egypt, Iraq, and remote villages in Ecuador withSephardic roots.^[7][8]

In 2011, it was reported that people with this syndrome in the Ecuadorian villages are resistant to cancer and diabetes and are somewhat protected against aging.^[7][9][10] This is consistent with findings in mice with a defective growth hormone receptor gene.^[8]

Treatment

Administration of GH has no effect on IGF-1 production, therefore treatment is mainly by biosynthetic IGF-1. IGF-1 must be taken before puberty to be effective.^[8]

IPLEX (Mecasermin rinfabate) is composed of recombinant human IGF-1 (rhIGF-1) and its binding protein IGFBP-3. It was approved by the U.S. Food and Drug Administration (FDA) in 2005 for treatment of primary IGF-1 deficiency or GH gene deletion.^[11][12] Side effects from IPLEX are hypoglycemia.

IPLEX’s manufacturing company, Insmed, can no longer develop proteins and can no longer manufacture IPLEX as of a statement released in January 2012.

Prognosis

People with Laron syndrome have strikingly low rates of cancer and diabetes.^[8]

Homo floresiensis

Recent publications have proposed that Homo floresiensis represented a population with widespread Laron syndrome.^[13][14] This hypothesis has received criticism and is unconfirmed.

Me: The main thing to take away from learning even more about dwarfism is that there are many factors and causes that can causes stunted growth and height but only a few that can results in tallness and increased height. For Laron Syndrome, the growth hormone receptors just don’t work properly so the entire growth process stops close to the very beginning. There is little IGF-1 or the IGF-1 transport proteins either. However, the people who are affected with this condition should still be able to possibility increase their height, not through the traditional growth hormone therapy ,but from stimulating the chondrocytes to proliferate in other ways that have been described on this website. 

What is really amazing for this type of dwarfism is that people who seem to be inflicted by this disorder have extremely low rates of cancer or diabetes, and seems to have very long life expectancies. 

Again another question that I thought of was this, “How much extra height is possible using the modern limb leg lengthening methods?”

This means that if we consider all of the surgeries that are out there right now, how much extra height can a person receive from the methods?

It seems that we first have to limit the range for the answer because some factors have to be taken into consideration. First, we assume that the person does not have an infinite amount of resources that can be disposed for just the purpose of limb lengthening surgery. I would guess that the wish of most people is not to increase in height, but to increase in the size of their wallet.

The surgery is expensive, takes a long time, involve a lot of pain, so the normal person would probably only be able to go through a surgery of this type, which is not based on some form of medical pathology but cosmetic, only once. If they really care about increasing their height, I might be able to see a person go through with the surgery twice. So we first assume the person has limited amount of money, time, and pain tolerance. They have enough money to go through with it at least once, which can range between $20,000-$120,000 depending one the type of sugary and surgical instrument they wanted to use.

It seems from reading the Make Me Taller forums that the maximum height increase possible using the instruments for each long bone is around 7-8 cm or 3 Inches. However, there are stories about Chinese surgeons who seem to be able to get upwards of 10 cms or 4 inches in the tibia or lower leg. However ,from the forums the general consensus is that a person can get 7-8 cms of extra length for their long bones. This means that the entire leg, for each leg, the person can increase their height by 16 cm or 6 inches total with one swift, major surgery reconstruction.

There was a member of the Make Me Taller forums and who was features on ABC News names Apotheosis who decided that one limb lengthening surgery was not enough, but went for a second round. I wrote in a previous post about him. Supposed he first increased his height from 5′ 6″-5’9″, a 3 cm or 7-8 cm increase which is what the surgeries allow for only one section of the leg.

Apotheosis went back and appeared to go for another round of surgery to increase his height by 5 inches the second time. This means that he increase his height by 8 inches to 6′ 2″. Of course, for a person like him who has the financial resources the time, and the determination to go through with such a thing, there seems to be no limit to how much taller they would want to be.

Conclusion: The instruments available can increase each long bone in a person’s limb by up to 7-8 cms, but there are stories of being able to increase by 10 cm which has not been validated. Of course, after the healing process and the bones have grown to the desired length, there is no one to stop a person to be like Apotheosis and go back to lengthen and increase in height some more.

I used to write up quite a few of these nice interesting articles that talks about the giants and the extreme bodies that have existed throughout human history. This will be a continuation of those series. So who is the tallest women in history?

Barring any mythical legends of lost tribes and civilizations, the tallest women in recorded history is Zeng Jinlian who doctors have calculated was 8 feet 1.75 inches (248.3 cm) tall if her severe spinal curvature was adjusted to be fully straight. That would make her the only female that has passed the 8 feet tall mark.

From the Tallest Man website HERE, the story of her life.

Zeng Jinlian (June 26, 1964 – February 13, 1982) was the tallest female ever recorded in medical history, taking Jane Bunford’s record. She is also the only female counted among the 16 individuals in medical history who reached a verified eight feet or more. At the time of her death at the age of 17, in Hunan, China, she was 8 ft 1.75 in (248.3 cm) tall. However, she could not stand up straight due to a severely deformed spine.

Nevertheless, she was the tallest person in the world at the time. In the year between the death of 8 feet 2 inch Don Koehler and her own, she surpassed fellow ‘eight-footers’ Gabriel Estavao Monjane and Suleiman Ali Nashnush. She was the second woman in recorded history to become the tallest person in the world. Jane Bunford was the first.

From Wikipedia HERE…

Zeng Jinlian (simplified Chinese: 曾金莲; traditional Chinese: 曾金蓮; pinyin: Zēng Jīnlián; June 25, 1965 – February 13, 1982) was the tallest woman ever verified in medical history, taking over Jane Bunford’s record. Zeng is also the only woman counted among the fourteen people who have reached verified heights of eight feet or more.

At the time of her death at the age of 17 in Hunan, China, Zeng, who would have been 8 feet, 1.75 inches (249 cm.) tall (she could not stand straight because of a severely deformed spine), was the tallest person in the world. In the year between Don Koehler’s death and her own, she surpassed fellow “eight-footers” Gabriel Estêvão Monjane and Suleiman Ali Nashnush. That Zeng’s growth patterns mirrored those of Robert Wadlow is shown in the table below.

As for the tallest women today who is still alive, that would go to Yao Defen, who stands at somewhere between 7′ 8″ and 7′ 9″, depending on which resource you wanted to use.

From the Wikipedia article HERE….

Yao Defen (Chinese: 姚德芬; pinyin: Yáo Défēn) of China, (born July 15, 1972) is the tallest living woman, as recognized byGuinness World Records.^[2] She stands 7 ft 8 in tall (2.33 m), weighs 200 kilograms (440 lb), and has size 26 (UK) / 78 (EU) feet.^[3][4][5] Her gigantism is due to a tumor in her pituitary gland.

Yao Defen was born to poor farmers in the town of Liuan in the Anhui province of Shucheng County. At birth she weighed 6.16 pounds. At the age of three years she was eating more than three times the amount of food that other three-year-old children were eating. When she was eleven years old she was about six feet, two inches tall. She was six feet nine inches tall by the age of fifteen years.[edit]Early life

The story of this “woman giant” began to spread rapidly after she went to see a doctor at the age of fifteen years for an illness. Medical doctor(who also saw her after years) properly diagnosed the illness, however decided not to cure her, because she and her family didn’t had 4000 yuan for the surgery(despite the official communism and socialism claims People’s Republic of China don’t have(and didn’t had) “free” or “social” public health service, except for high government officials). ^[6]After that, many companies attempted to train her to be a sports star. The plans were abandoned, however, because Defen was too weak. Because she is illiterate, since 1992 Yao Defen has been forced to earn a living by traveling with her father and performing.

Yao Defen’s giant stature was caused by a large tumor in the pituitary gland of her brain, which was releasing too much growth hormone and caused excessive growth in her bones. Six years ago, a hospital in Guangzhou Province removed the tumor, and she stopped growing.

The tumor returned and she was treated in Shanghai in 2007, but was sent home for six months with the hope that medication would reduce her tumor enough to allow surgery. The second surgery was never performed due to lack of funds.

In 2009, the TLC cable TV network devoted a whole night’s show to her. She suffered from a fall in her home and had internal bleeding of the brain. She recovered and felt some happiness after a visit from China’s tallest man, Zhang Juncai.

Medical help

A British television program filmed a documentary on her and helped raise money so she could get proper medical care. They measured her and according to the documentary she is seven feet, eight inches tall. Two leading doctors in acromegaly agreed to help Yao. She was taken to a nearby city hospital, where imaging procedures revealed that a small portion of her tumor, thought to have been removed many years before, still remained, causing continuing problems including weakening vision as it pressed against her optic nerve. She returned home, then was admitted for a month under observation in the larger Shanghai Ruijin Hospital, and given dietary supplements. In that hospital, her growth hormone was greatly slowed down, although it is still a problem. Upon her return home to her mother and brother, she was able to walk with crutches, unassisted by others, and was given a six-month supply of medicines and supplements in hopes of improving her condition enough to undergo surgery.

Acromegaly

Yao currently suffers from hypertension, heart disease, poor nutrition, and osteoporosis. Acromegaly often results from a tumor within the pituitary gland that causes excess growth hormone secretion. As a result, the body’s features become enlarged. It can also delay the onset of puberty as is the case with Yao. She has nosecondary sexual characteristics. Potential complication lacking surgery includes blindness and eventually premature death.

She lives near her mother (who is only four feet, eight inches tall) in a small village in rural China.

From the Tallest Man website HERE…

Yao Defen – 7 feet 8 inches (233.7 cm)