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"Is Growth Hormone the Fountain of Youth?"
Growth Hormone: Its Side-Effects and Benefits.
Overview
Consciously, or not, what most athletes are striving for by training is to elevate their anabolic (growth-promoting) hormone levels. Growth hormone, also known as somatotropin, is our most important anabolic hormone possessing both developmental and metabolic properties.
Developmental: During our initial decades of life growth hormone is principally responsible for the growth of bones and muscles. Beyond 30 years of age, however, our growth hormone levels begin to decline and is associated with a steadily loss of muscle mass and bone reabsorption.
Metabolic: Another major role of growth hormone is to regulate which substrates are used for energy production. Growth hormone mobilizes lipids (fats) for energy usage. Amino acids (proteins), on the other hand, are spared from being used as energy substrates under the influence of growth hormone. Growth hormone thus keeps our fat reserves at a healthy minimum and our muscle content high. In other words, growth hormone effectively promotes the development of lean (fat free) muscle. In fact, the "pot-belly" that appears in most males during their 30's is a function of this age-related reduction in growth hormone.
Anti-Aging: There is currently a lot of excitment about the possibility of growth hormone replacement as an anti-aging therapy. Athletes are also looking for ways to increase their growth hormones levels in order to build more muscle and reduce body fat.
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Central Nervous System Release
The Hypothalamus is a part of the brain that serves to integrate and respond to information it receives from the rest of the body. In particular, the hypothalamus exerts control over the secretions of the Anterior Pituitary, a small gland located at the base of our brains. The pituitary is also commonly referred to as the Master Gland, which should give you some idea of its importance. Therefore, the hypothalamus, via its direct control over the anterior pituitary, indirectly governs the body's growth and metabolic processes.
Rather than a steady stream, however, growth hormone is released from the anterior pituitary in spurts due to the competing actions of stimulatory and inhibitory factors originating from the hypothalamus.
Hypothalamic Factors
Stimulatory: Growth Hormone Releasing Hormone, or GHRH, produced by the hypothalamus stimulates the anterior pituitary to secret growth hormone.
Inhibitory: Somatostatin antagonizes the release of growth hormone from the anterior pituitary. Like GHRH, somatostatin is produced in the hypothalamus from where it acts on the anterior pituitary.
Regulatory Feedback
Growth hormone is not wasted. Once secreted into the blood stream growth hormone inhibits its further release from the anterior pituitary (and hypothalamus). The net result is that growth hormone release is favored when its levels are low and is inhibited when it is present in adequate amounts. This is a classical case of negative feedback and prevents the overproduction of growth hormone; a biologically economic measure.
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Regulators of Release
Age-Dependence: Growth hormone levels are highest during puberty. Accordingly, this is when we are growing the most rapidly. After about 30 years of age our growth hormone levels begin to decline at a rate of about 14% per decade.
Translating this into practical terms..., if we were producing 500 micrograms of growth hormone per day at 20 years, we would be producing only about 25 micrograms per day by the time we reach 80!
It is now commonly thought that an increase in circulating somatostatin underlies this age-related reduction in growth hormone production.
Sleep-Dependence: After an hour, or so, of initiating sleep we enter into a mode of deep sleep known as Slow Wave Sleep, or SWS. SWS occurs only during the initial hours of sleep and appears to be inhibited as the night progresses.
We build muscle while we sleep... Growth hormone is principally released from the anterior pituitary during moments of SSW. Therefore, anything that interferes with our SSW will likewise interfere with the release of growth hormone. Alcohol, in particular, interrupts SSW and consequently will also inhibit the release of growth hormone from the anterior pituitary.
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Note: I would discourage young athletes who are serious about gaining muscle mass, from consuming alcohol, at least immediately before bed or after exercise (see below).
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Exercise-Dependence: Growth hormone is also released following exercise. This aspect of growth hormone release is extremely important for muscle recovery following exercise. Excessive exercise, however, shocks our system into producing somatostatin. Recall that somatostatin inhibits growth hormone release and causes muscle breakdown. Therefore, over doing it in the weight room can actually lead to muscle degradation rather than muscle growth.
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Note: Sensible exercise and adequate rest go hand in hand in building muscle.
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Other Releasers: Growth hormone is also released in response to these other physiological stimuli:
- Fasting
- Low blood sugar
- Stress
- Injury or Trauma
- Fever
- Dopaminergic Agonists (Neurotransmitters)
- L-arginine?
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Effects of Growth Hormone
Direct Effects: Growth Hormone
Growth Hormone Receptors: Growth hormone directly activates cells expressing growth hormone receptors on their surface. These receptors bind growth hormone after being released from the Anterior Pituitary into the blood stream. The binding of growth hormone to the receptor activates the cell.
Fat Reserves: Fat cells (adipocytes) express high levels of growth hormone receptor. The binding of growth hormone to these receptors causes the adipocyte to release lipids into the blood stream and simultaneously prevents them from taking up lipids from the exterior. In other words, growth hormone mobilizes fats for energy usage. The ultimate result is that our fat reserves dwindle when growth hormone levels are high.
Growth hormone also slows the use of glucose for energy metabolism.
Indirect Effects: Insulin-like Growth Factor-1
The majority of growth hormone's actions, however, are indirect.
The majority of growth hormone's effects are mediated by Insulin-like Growth Factor 1, or IGF-1. IGF-1 is produced by the liver when stimulated by growth hormone; liver cells (hepatocytes) also express high levels of growth hormone receptor.
Therefore, increases in growth hormone are commonly mirrored by increases IGF-1. When the growth hormone receptor isn't functioning properly, however, IGF-1 levels are low relative to growth hormone.
Muscle Growth: IGF-1 causes muscle cells (myocytes) to increase protein production (synthesis), reduce protein breakdown, take up amino acids (building blocks of proteins) and to divide (proliferate). In other words, our muscles grow when stimulated by IGF-1.
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Bone Growth: Bone cells (chondrocytes) also respond to IGF-1 by proliferating; our bones grow. Connective tissue and cartilage also increase in response to IGF-1.
Kidneys: Our kidneys and internal organs increase in size in response to IGF-1.
Regulatory Feedback: Recall that growth hormone eventually shuts off its own release through a process of regulatory feedback. Well, IGF-1 also feedsback upon the hypothalamus and anterior pituitary to inhibit further growth hormone release. More precisely, IGF-1 promotes the release of somatostatin from the hypothalamus, as well as directly inhibits growth hormone release from the anterior pituitary.
Creatine Supplementation: Intriguing data has just appeared indicating that creatine supplementation increases IGF-1 expression independently of an exercise stimulus, an effect most likely downstream of an enhancement of methylation status. Click here to read the issue of the Creatine Newsletter that discusses these provocative studies.
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Growth Hormone Disorders
There are numerous conditions associated with alterations of growth hormone production or receptor recognition.
Too little Growth Hormone or Deficiency
Childhood--Dwarfism: Dwarfism results if the liver and other target tissues are not sufficiently stimulated by growth hormone. This condition arises because either too little growth hormone is produced during childhood, or because the growth hormone receptors expressed by cells are non-functional. Under conditions where the growth hormone receptor isn't functioning properly, IGF-1 levels are low in comparison to growth hormone.
Mental retardation is also commonly observed in cases of growth hormone deficiency (GHD). Other symptoms of GHD resemble the normal aging process.
Adulthood--Growth Hormone Deficiency (GHD): Adult onset GHD is characterized by reduced lean body mass, bone density and strength, while visceral fat and mortality, principally due to cardiovascular disease, increases. A characteristic elevation in plasma cholesterol (high LDL/low HDL) is most likely responsible for the increased incidence of cardiovascular disease in GHD patients. Insulin resistance is also frequently encountered. This condition frequently results from the medical intervention of a Pituitary tumor with resultant loss of the growth hormone producing cells, or Somatotropes.
Adulthood--Normal Aging: We are all familar with the belly that "often" forms in males after the age of 30 year. This increase in body fat is in large part due to a age-dependent decrease in growth hormone.
The reduction in growth hormone with age is associated with increased body fat, and reduced muscle mass and bone density. This is a clinical condition referred to as Somatopause. Other aspects of the normal aging process that is correlated with a reduction of growth hormone are cardiovascular disease, wrinkling, gray hair, decreased energy, and reduced sexual function. Many of these same symptoms are present in younger adults with GHD.
Too Much Growth Hormone or Overabundance
Too much growth hormone can have different effects depending on the age at which it occurs. Alarmingly, reduced life expectancy is frequently encountered in natural disorders where growth hormone levels are abnormally elevated.
Childhood--Giagantism: An overabundance of growth hormone during childhood or adolescence gives rise to giagantism. It is a very rare condition that usually results from a tumor of the cells that produce growth hormone.
Adulthood--Acromegaly: Acromegaly results from an excess of growth hormone (ie, IGF-1) during adulthood. IGF-1 is responsible for longitudinal growth (increase in height) during childhood and adolescence. However, an excess of IGF-1 during adult life (after our bones have stopped elongating) causes bones to widen and increase in girth. This disfigures our features, particularly in the face (large square jaw), hands and feet.
Glucose intolerance is also commonly observed in acromegliacs. In fact, about one quarter of all acromegliacs develop diabetes mellitus due to peripheral resistance to insulin
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Replacement Therapy
This is a field that is still in its infancy. Previously, human growth hormone was isolated directly from the anterior pituitary of cadavers. This approach yielded extremely small amounts of painfully expensive growth hormone. With the recent advent of genetic engineering, recombinant growth hormone can now be produced more economically in bacteria. Although this has reduced the cost considerably, it is still expensive.
Use in Growth Hormone Deficiency (GHD)...
Children: GHD in children is most noticeably characterized by stunted growth. Recombinant growth hormone is often used in children with GHD to augment growth.
Adults: Increases in bone density and lean body mass are often observed in patients with adult-onset GHD when treated with recombinant growth hormone. Plasma cholesterol has also been observed to stabilize (low LDL/high HDL).
Use in Normal Individuals...
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Eldery: Some studies have shown that recombinant growth hormone treatment in the elderly may actually reverse some of these signs of aging. In particular, an increase in lean body mass is commonly observed. In some cases a reduction in serum cholesterol is also documented. Unfortunately, adverse side effects are also sometimes encountered and may include edema, fluid retention and carpal tunnel syndrome.
Athletes: In adults recombinant growth hormone has been shown to increase lean body mass. This has led to the notion that growth hormone might be used to enhance physical performance in athletes. Interestingly, although growth hormone treatment in adults frequently increases lean body mass, increases in strength are more difficult to prove. Furthermore, fluid retention and enlargement of some internal organs contribute significantly to the observed increase in lean body mass. Finally, it is still an open issue whether the use of recombinant growth hormone causes acromegaly in athletes.
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Scientific Reference
Conceicao F.L., Bojensen A., Lunde Jorgensen J.O., Christiansen J.S. (July 2001) Growth hormone therapy in adults. Frontiers in Neuroendocrinology Volume 22 (3): pages 213-246.
Selected Website
Growth Hormone Physiologic Effects of Growth Hormone.
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