Vol.3, # 12
April 1, 2006

Q: What is human growth hormone and what does it do? - Layperson

A: Human Growth Hormone(HGH) is produced by the pituitary gland in the center of the brain. Everyone naturally has HGH in their body from birth. During adolescence, when we are at an optimal youthful condition, production of HGH is high. However, your HGH levels peak somewhere between the ages of 21 and 30 and then aggressively decline at the alarming rate of 14% per decade.

Research has shown that virtually every adult is HGH deficient. By the age of 40 you may already have “elderly” levels of HGH production, down as much as 50% of youthful levels.

Growth hormone, also known as somatotropin, is a protein hormone of about 190 amino acids that is synthesized and secreted by cells called somatotrophs in the anterior pituitary. It is a major participant in control of several complex physiologic processes, including growth and metabolism. Growth hormone is also of considerable interest as a drug used in both humans and animals.

Structure and gene of the human GH molecule

The genes for human growth hormone are localized in the q22-24 region of chromosome 17 and are closely related to human chorionic somatomammotropin (hCS, also known as placental lactogen) genes. GH, human chorionic somatomammotropin (hCS), and prolactin (PRL) are a group of homologous hormones with growth-promoting and lactogenic activity.

Human growth hormone is a protein of 191 amino acids and a molecular weight of about 22,000 daltons. The structure includes four helices necessary for functional interaction with the GH receptor. GH is structurally and apparently evolutionarily homologous to prolactin and chorionic somatomammotropin. Despite marked structural similarities between growth hormone from different species only human and primate growth hormones have significant effects in humans.

Secretion of GH

GH is secreted into the blood by the somatotrope cells of the anterior pituitary gland, in larger amounts than any other pituitary hormone. The transcription factor PIT-1 stimulates both the development of these cells and their production of GH. Failure of development of these cells, as well as destruction of the anterior pituitary gland, results in GH deficiency.

Peptides released by neurosecretory nuclei of the hypothalamus into the portal venous blood surrounding the pituitary are the major controllers of GH secretion by the somatotropes. Growth hormone releasing hormone (GHRH) from the arcuate nucleus and ghrelin promote GH secretion, and somatostatin from the periventricular nucleus inhibits it. GH secretion is also affected by negative feedback from circulating concentrations of GH and IGF-1.

Although the balance of these stimulating and inhibiting peptides determines GH release, this balance is affected by many physiological stimulators and inhibitors of GH secretion. Stimulators of GH secretion include (among others) sleep, exercise, hypoglycemia, dietary protein, and estradiol. Inhibitors of GH secretion include dietary carbohydrate and glucocorticoids.

Most of the physiologically important GH secretion occurs as several large pulses or peaks of GH release each day. The plasma concentration of GH during these peaks may range from 5 to 30 ng/mL or more. Peaks typically last from 10 to 30 minutes before returning to basal levels. The largest and most predictable of these GH peaks occurs about an hour after onset of sleep. Otherwise there is wide variation between days and individuals. Between the peaks, basal GH levels are low, usually less than 3 ng/mL for most of the day and night.

The amount and pattern of GH secretion change throughout life. Basal levels are highest in early childhood. The amplitude and frequency of peaks is greatest during the pubertal growth spurt. Healthy children and adolescents average about 8 peaks per 24 hours. Adults average about 5 peaks. Basal levels and the frequency and amplitude of peaks decline throughout adult life.

Several molecular forms of GH circulate. Much of the growth hormone in the circulation is bound to a protein (growth hormone binding protein, GHBP) which is derived from the growth hormone receptor.

Physiologic Effects of Growth Hormone

A critical concept in understanding growth hormone activity is that it has two distinct types of effects:

  • Direct effects are the result of growth hormone binding its receptor on target cells. Fat cells (adipocytes), for example, have growth hormone receptors, and growth hormone stimulates them to break down triglyceride and supresses their ability to take up and accumulate circulating lipids.
  • Indirect effects are mediated primarily by a insulin-like growth factor-I (IGF-I), a hormone that is secreted from the liver and other tissues in response to growth hormone. A majority of the growth promoting effects of growth hormone is actually due to IGF-I acting on its target cells.

Keeping this distinction in mind, we can discuss two major roles of growth hormone and its minion IGF-I in physiology.

Effects on Growth

Growth is a very complex process, and requires the coordinated action of several hormones. The major role of growth hormone in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-I. IGF-I stimulates proliferation of chondrocytes (cartilage cells), resulting in bone growth. Growth hormone does seem to have a direct effect on bone growth in stimulating differentiation of chondrocytes.

IGF-I also appears to be the key player in muscle growth. It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues.

Metabolic Effects

Growth hormone has important effects on protein, lipid and carbohydrate metabolism. In some cases, a direct effect of growth hormone has been clearly demonstrated, in others, IGF-I is thought to be the critical mediator, and some cases it appears that both direct and indirect effects are at play.

  • Protein metabolism: In general, growth hormone stimulates protein anabolism in many tissues. This effect reflects increased amino acid uptake, increased protein synthesis and decreased oxidation of proteins.

  • Fat metabolism: Growth hormone enhances the utilization of fat by stimulating triglyceride breakdown and oxidation in adipocytes.

  • Carbohydrate metabolism: Growth hormone is one of a battery of hormones that serves to maintain blood glucose within a normal range. Growth hormone is often said to have anti-insulin activity, because it supresses the abilities of insulin to stimulate uptake of glucose in peripheral tissues and enhance glucose synthesis in the liver. Somewhat paradoxically, administration of growth hormone stimulates insulin secretion, leading to hyperinsulinemia.

Control of Growth Hormone Secretion

Production of growth hormone is modulated by many factors, including stress, exercise, nutrition, sleep and growth hormone itself. However, its primary controllers are two hypothalamic hormones and one hormone from the stomach:

  • Growth hormone-releasing hormone (GHRH) is a hypothalamic peptide that stimulates both the synthesis and secretion of growth hormone.

  • Somatostatin (SS) is a peptide produced by several tissues in the body, including the hypothalamus. Somatostatin inhibits growth hormone release in response to GHRH and to other stimulatory factors such as low blood glucose concentration.

  • Ghrelin is a peptide hormone secreted from the stomach. Ghrelin binds to receptors on somatotrophs and potently stimulates secretion of growth hormone.

Growth hormone secretion is also part of a negative feedback loop involving IGF-I. High blood levels of IGF-I lead to decreased secretion of growth hormone not only by directly suppressing the somatotroph, but by stimulating release of somatostatin from the hypothalamus.

Growth hormone also feeds back to inhibit GHRH secretion and probably has a direct (autocrine) inhibitory effect on secretion from the somatotroph.

Integration of all the factors that affect growth hormone synthesis and secretion lead to a pulsatile pattern of release. Basal concentrations of growth hormone in blood are very low. In children and young adults, the most intense period of growth hormone release is shortly after the onset of deep sleep.

Disease States

States of both growth hormone deficiency and excess provide very visible testaments to the role of this hormone in normal physiology. Such disorders can reflect lesions in either the hypothalamus, the pituitary or in target cells. A deficiency state can result not only from a deficiency in production of the hormone, but in the target cell's response to the hormone.

Clinically, deficiency in growth hormone or receptor defects are as growth retardation or dwarfism. The manifestation of growth hormone deficiency depends upon the age of onset of the disorder and can result from either heritable or acquired disease.

The effect of excessive secretion of growth hormone is also very dependent on the age of onset and is seen as two distinctive disorders:

  • Giantism is the result of excessive growth hormone secretion that begins in young children or adolescents. It is a very rare disorder, usually resulting from a tumor of somatotropes. One of the most famous giants was a man named Robert Wadlow. He weighed 8.5 pounds at birth, but by 5 years of age was 105 pounds and 5 feet 4 inches tall. Robert reached an adult weight of 490 pounds and 8 feet 11 inches in height. He died at age 22.

  • Acromegaly results from excessive secretion of growth hormone in adults. The onset of this disorder is typically insideous. Clinically, an overgrowth of bone and connective tissue leads to a change in appearance that might be described as having "coarse features". The excessive growth hormone and IGF-I also lead to metabolic derangements, including glucose intolerance.

Pharmaceutical and Biotechnological Uses of Growth Hormone

In years past, growth hormone purified from human cadaver pituitaries was used to treat children with severe growth retardation. More recently, the virtually unlimited supply of recombinant growth hormone has lead to several other applications to human and animal populations.

Human growth hormone is commonly used to treat children of pathologically short stature. There is concern that this practice will be extended to treatment of essentially normal children - so called "enhancement therapy" or growth hormone on demand. Similarly, growth hormone has been used by some to enhance atheletic performance. Although growth hormone therapy is generally safe, it is not as safe as no therapy and does entail unpredictable health risks. Parents that request growth hormone therapy for children of essentially-normal stature are clearly misguided.

The role of growth hormone in normal aging remains poorly understood, but some of the cosmetic symptoms of aging appear to be amenable to growth hormone therapy. This is an active area of research, and additional information and recommendations about risks and benefits will undoubtedly surface in the near future.

Growth hormone is currently approved and marketed for enhancing milk production in dairy cattle. There is no doubt that administration of bovine somatotropin to lactating cows results in increased milk yield, and, depending on the way the cows are managed, can be an economically-viable therapy. However, this treatment engenders abundant controversy, even among dairy farmers. One thing that appears clear is that drinking milk from cattle treated with bovine growth hormone does not pose a risk to human health.

Another application of growth hormone in animal agriculture is treatment of growing pigs with porcine growth hormone. Such treatment has been demonstrated to significantly stimulate muscle growth and reduce deposition of fat.

 
Studies published in the New England Journal of Medicine prove that HGH can:
  • Shed Bodyfat
  • Increase Muscle Tone
  • Boost your Energy, Strength, and Endurance
  • Reduce Wrinkles and Create Tighter, Smoother Skin
  • Help you Sleep Better
  • Improve Sex Drive and Performance
  • Improve Immune and Heart Function, Bone Density, Healing Time and Cholesterol
  • Improve Brain Function, Memory and Mental Focus
 

CATEGORY 1:
Non-Homeopathic Rejuvenation Products

The majority of natural HGH products are referred to as “HGH releasers”, “HGH Precursors” and “HGH Secretagogues”. Most of these products are nothing more than glorified amino acid supplements that have been around forever that are now trying to capitalize on the popularity of HGH at over-inflated prices. Not only do they normally CONTAIN NO INGREDIENTS THAT OPTIMIZE PITUITARY AND LIVER FUNCTION, THE TWO GLANDS INVOLVED IN HGH PRODUCTION, but according to a very informative book by Dr. H.A. Davis dealing with natural supplementation:

“30% of patients tested DO NOT respond these GH...‘releasers’ or ‘secretagogues’. They have been around a long time and, in many cases, have never yielded the same quality and consistent results.”

Dr. Davis concluded he felt that homeopathy is the safest, most sophisticated form of natural supplementation by combining “years of scientific research with the benefits of safety and effectiveness." I agree with Dr. Davis. Homeopathy has been around for over centuries and has an incredible track record of sound medical science, safety and effectiveness.

That brings us to two types of homeopathic products that I found, (1) Homeopathic formulas without ingredients that address healthy liver function and (2) Homeopathic formulas with ingredients that address healthy liver function. For the reasons you’ll see below, I can only recommend one of the two. Take a look.

CATEGORY 2:
Homeopathic Formulas Without an Ingredient to
Address Healthy Liver Function

I cannot recommend this type of product. Once you understand how critical the liver is to your health, which we’ll discuss in Category 3 below, you’ll understand why.

CATEGORY 3:
Homeopathic Formulas That Include Ingredients to
Address Healthy Liver Function

My research led me to the strong conclusion that this type of product is the best natural option you can buy. Let’s face it, there are many products that may provide multiple rejuvenating benefits, but if you find one that gives you those rejuvenating benefits AND has been formulated to provide healthy liver support, that’s an unbeatable combination.

As a doctor, it’s safety and health first, and everything else second. Take one quick look at the importance of healthy liver function and all the things that your liver is responsible and you’ll instantly understand why I think this is so important for rejuvenation, long-term health and prevention.

A healthy liver is so important that you can only survive for a few days if it shuts down—if the liver fails, your body will fail, too. It does many important things to make sure everything runs smoothly. Here’s a partial list of what your liver does:

  • Helps digest food and absorb nutrients from the food you eat including vitamins, sugars and other nutrients for optimum health and energy
  • Produces immune factors to combat infection and keep you healthy
  • Breaks down and removes harmful substances, like alcohol, drugs, bacteria and other toxic (poisonous) substances from your body
  • Makes sure that your body has just the right amount of other chemicals that it needs for healthy function
  • Controls the production and removal of cholesterol
  • Helps control bleeding by making clotting factors

The problem is that our organs weaken and shrink with age and the liver is one of the  largest organs in your body. Given that there are homeopathic formulas that do address healthy liver function, why waste your time with one that doesn’t?Human Growth Hormone is expensive: the costs vary from $75 to $200 per week. The dosage is tailored to the individual's need: someone who is healthy and is using HGH for prevention will need much less than the individual with no pituitary function, dilated cardiomyopathy, or severe fatigue/fibromyalgia/lupus!

Monitoring HGH is done with a serum assay of Somatomedin-C (also named Insulin Like Growth Factor-1 [IGF-1]. Without appropriate monitoring, there is no way of adequately evaluating progress or hormonal replacement.

AT THE PRESENT TIME,
THERE IS NO PROVEN REPLACEMENT REGIMEN
FOR HUMAN GROWTH HORMONE EXCEPT
INJECTABLE HGH

Understanding the Role of Oral Supplements and HGH
AMINO ACIDS
Studies in young adults show that at least four amino acids can cause the release of up to 9 times as much HGH over a short period of time. Those amino acids are:

  1. L-glutamine: 9 grams
  2. L-arginine: 4 grams
  3. L-ornithine: 4 grams
  4. L-lysine: 2 grams

There are two problems with these studies. First, the amount of increase in growth hormone is of short duration and no long term increase in IGF-1 has been reported. And more importantly, these studies have not been performed in men and women over 50 years of age. It is a fact that the best releaser of HGH is strong exercise, and secondly a good night sleep-- yet, neither cause the additional release of HGH in men over 60 years of age.

There are now a number of advertisements for oral HGH preparations. The problem with these is that only a rare individual can raise his or her IGF-1 levels to 350 ug/ml, which is the target for replacement. Why spend hundreds of dollars if your IGF-1 level does not reach adequate levels?Chose one that works for you.



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DISCLAIMER:  The information in this column, is NOT intended to diagnose and/or treat any health related issues and is provided solely for informational purposes only. Consult the appropriate healthcare professional before making any changes to your healthcare regime. Even what may seem like simple changes in the diet for example, can interact with, and alter, the efficiency of medications and/or the body's response to the medications. Many herbs and supplements exert powerful medicinal effects. Neither the author, nor the website designers, assume any responsibility for the reader's use or misuse of this information.

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