General Information about Growth Hormone
You may have ever heard about growth hormone 1 (somatotropin) and growth hormone 2. These are genes for the human growth hormone which are localized in the q22-24 region of chromosome 17 and are connected with placental lactogen (chorionic somatomammotropin) genes. These placental lactogen genes, GH and prolactin make up a group of homologous hormones with growth-increasing and lactogenic function.
Growth Hormone Structure
The primary component of human GH structure is a protein of 191 amino acids and a molecular weight of 22,124 daltons. Human growth hormone also has in its structure four helices that are important for functional interconnection with its receptor. It has been proven that in its structure human growth hormone is homologous to prolactin and placental lactogen genes. Despite the fact that growth hormones of different species have some likeness in structure, only growth hormone of a man and Old World monkey have significant influence on the receptor of human GH.
Some of GH molecular isoforms are in the pituitary gland and are released in the blood. In particular, one variant of about 20 kDa arise by alternative splicing is a fairly constant ratio of 1:9, and more recently it has been found a further variant ~ 23-24 kDa in post-training condition in large proportions. This variant has not been found, but it is supposed that it coincides with a 22 kDa glycosylated variant of 23 kDa found in the pituitary gland.
Furthermore, a protein that is also known as growth hormone-binding protein, or simply GHBP and is the cut part of the growth hormone receptor, and an acid-labile subunit (ALS) is connected with these variants.
The neurosecretory nuclei of the hypothalamus are responsible for regulation of growth hormone secretion. In hypophyseal portal venous blood that surrounds the pituitary such cells secrete peptides of growth hormone-releasing hormone (GNRH or it is also called somatocrinin) and growth hormone inhibiting hormone (GHIH or is also named as orsomatostatin).
GH-release in the pituitary gland first and foremost is defined by the balance of these two peptides, which in turn depends on many physiological stimulators (e.g., exercise, eating, sleeping), and inhibitors (e.g., free fatty acids) of GH secretion.
Growth hormone cells of anterior pituitary lobe then synthesize and secrete growth hormone in a pulsating manner, in reply to these stimuli in the hypothalamus. The biggest and the most predictable of these GH peaks happens approximately in one hour after sleep onset with plasma levels of 13 to 72 ng per ml.
In other case there is a big variation between days and individuals. Almost fifty percent of GH secretion takes place during the third and fourth sleep phases of NREM. Bursts of secretion take place throughout the day from 3 to 5 hour intervals. The plasma concentration of GH during these peaks may be between 5 and even 45 ng per ml. Basal GH levels are not so great during these bursts intervals, as usual it is not more than 5 ng/mL for the most part of the day and night. One more test of the pulsatile profile of GH has shown in all of them no more than 1 ng/ml for basal levels while maximum bursts were situated around 10-20 ng/mL.
As usual human growth hormone is influenced by following factors: age, sex, diet, trainings, stress, and some other hormones. Young teenagers produce GH nearly about 700 μg per day, while strong healthy adults produce it in a number of about 400 μg per day. Deprivation of sleep usually inhibits the release of GH, especially after early adulthood.
The principle means of endocrine regulation of growth.
The influence that human growth hormone exerts on the body’s tissues can be generally named as anabolic or the building up effect. It affects with the same principle as other protein hormones do: human growth hormone interacts with a special receptor on the cells’ surface.
The most common growth hormone effect is an increased height of a child. It happens due to the fact that the height is stimulated by two following mechanisms:
- due to the fact that polypeptide hormones cannot be soluble in fat, they appear to not be able to penetrate cell membranes. So, human growth hormone affects the body by connecting to receptors on target cells, where it activates the MAPK/ERK pathway. In such a way growth hormone directly stimulates division and multiplication of cartilage chonodrocytes.
- growth hormone also exerts its effect through JAK-STAT signaling way, producing insulin-like growth factor 1 (IGF-1, also called as somatomedin C), a hormone that is homologous to proinsulin. The main target organ for human growth hormone stimulation and also it is a major site for production of IGF-1. It has strong growth-stimulating impact on a great number of tissues. Complementary IGF-1 is produced within target tissues, thus making it both an endocrine and an autocrine/paracrine hormone. Furthermore, IGF-1 has an ability to affect stimulatory osteoblast and chondrocyte activity to increase growth of bone.
Despite the fact that the growth hormone increases height in children and adults, it also may exert many other influences on the body.
Importance of GH in Medicine
Abundance of GH
If there is an abundance of GH in the body it causes a pituitary tumor composed of GH cells of the anterior pituitary gland. Such GH adenomas are increased slowly and little by little produce a great amount of GH. Last investigations show that most of all medical problems are due to GH abundance in the body. Moreover, this GH adenoma as been grown to a big size may cause headaches, bad vision due to the fact that it influences optic nerves. Also it can cause lack of other pituitary hormones by offset.
If GH is produced in excess amounts for a long period of time, it may cause thickening of jaw, fingers and toes bones. Heaviness of the jaw and increased size of digits that are results of such thickening has a special name in medicine and it is an acromegaly. Moreover, it can cause addition problems such as sweating, influence on nerves (e.g. carpal tunnel syndrome), muscle illness, excess sex hormone-binding globulin (SHBG), insulin resistance or even a rare form of type 2 diabetes, and decreased sexual function.
Tumors that are caused by GH-secretion are usually found by doctors when an ill person is nearly 50 years old. Such a tumor does not typically appear in the childhood but if it occurs, great number of GH can provoke an excessive growth, often named as pituitary gigantism.
The only effective treatment for such tumors caused by GH is a surgical removal. However, sometimes it can be treated (or at least block function) with the help of focused radiation or a GH antagonist such as pegvisomant. Furthermore, some medications such as octreotide (somatostatin agonist) and bromocriptine (dopamine agonist) can be taken to block GH secretion because both somatostatin and dopamine negatively decrease GHRH-mediated GH release from the anterior pituitary gland.
Deficiency of GH
Human growth hormone deficiency can cause a lot of problems that depend on the age at which they appear. In childhood, GH deficiency may cause growth decrease and short stature including genetic conditions and congenital malformations. During adult life GH deficiency is rarely met but if it occurs, it may cause adenomas and continuation of childhood problems, other structural lesions or trauma, and sometimes idiopathic GHD.
Those adults who suffer GH deficiency may suffer from excessive fat mass and decreased muscle mass. They often feel a lack of energy and decreased quality of life.
In order to determine GH deficiency at time you need to make a multiple-step diagnostic process, usually including GH stimulation tests to define whether the patient's pituitary gland will release a pulse of GH when provoked by various stimuli.
Quality of life
Some studies that were conducted on people with human growth hormone deficiency have shown that GH greatly affects mental and emotional state of a person and increases energy level. Those people who have human growth hormone deficiency usually suffer from depression while those who have normal amount of GH do not. The treatment of depression presupposed a treatment of growth hormone deficiency. However, long-term effects of such treatment are still unknown.
Many researches have proven that human growth hormone also affects cognitive function. Studies were carried out in terms of learning and memory investigations. Growth hormone may be useful in the treatment of people with GH deficiency that caused cognitive impairment.
Treatment with the help of GH is carried out only under certain circumstances, and needs regular monitoring due to often and bad side effects. Human growth hormone is taken as replacement therapy in people with GH deficiency of either childhood-onset or adult-onset (usually as a result of an appeared pituitary tumor). As usual in treated people the beneficial results of treatment are as follows: decreased fat mass, increased lean muscle mass, increased bone density, increased lipid profile, decreased cardiovascular risk factors, and good impact on psychological state.
GH in sports
Naturally, human growth hormone is produced by human body. Usually exogenous human growth hormone is used in medicine for different medical purposes. However, it was discovered by athletes and they start to increase human growth hormone in their bodies in order to improve performance. Until 1981 when recombinant human growth hormone (rHGH) was made, HGH was only accessible from corpses.
The discovery of recombinant human growth hormone along with other peptide hormone progress enlarged the accessibility of human growth hormone on legal market and on black ones too. The first information about the use of growth hormone by athletes appeared in 1982 in California. It was Dan Duchaine’s “Underground Steroid handbook”. It is not actually known where and when human growth hormone was used in such a way.
It was in 1989 when International Olympic Committee prohibited a human growth hormone on competition for the first time. Despite the fact that human growth hormone is a prohibited substance and is considered as illegal for sport purposes, nowadays exceed of HGH is present in all fields of sport. It can be explained by a fact that human growth hormone is more difficult to reveal than other anabolic steroids.
Athletes from different kinds of sport such as power sports, bodybuilding, professional wrestling, mixed martial arts, swimming, baseball, strength sports, track and field, cycling, soccer, weight lifting, skiing and endurance sports were noticed to abuse human growth hormone. Moreover, they used it in combination with other performance-enhancing products such as androgenic anabolic steroids and also testosterone, and those drugs that have an ability to increase HGH and erythropoietin.
In fact, there are no proves and serious trials that could show that human growth hormone really positively affects athletes performance and does not cause bad side effects. There were only few studies and some of them have been recently reviewed and analyzed in a meta-analysis.
Despite the fact that authors consider this meta-analysis as too limited since only few of the included studies investigated athletic performance and by the fact that reviews in the studies may not reflect realistic doses and regimens, below there is a conclusion from these studies:
"Claims that growth hormone enhances physical performance are not supported by the scientific literature. Although the limited available evidence suggests that growth hormone increases lean body mass, it may not improve strength; in addition, it may worsen exercise capacity and increase adverse events. More research is needed to conclusively determine the effects of growth hormone on athletic performance."
As for side effects of the drug there is a citation from animal studies: "long-term administration of human growth hormone can increase the risk of diabetes, retention of fluids, joint and muscle pain, hypertension, cardiomyopathy, osteoporosis, irregular menstruation, impotence and elevated HDL cholesterol."
A review from the United States House Committee on Oversight and Government Reform on steroid and human growth hormone use has discovered that the inappropriate use of HGH by professional athletes and amateurs was provoking the industry that make the drug for the general public for medically prohibited use.
Lean body mass
The study that were carried out concluded that human growth hormone decreases body fat and raises lean body mass. Unfortunately, there was no improvement in muscle strength observed. It can be explained by the fact that fluid stays in the organism only for a short period of time.
Nowadays there is no consensus among the scientists whether human growth hormone makes larger the most visible muscles. However, it should be mentioned there is a difference between muscle mass and muscle strength.
One group of researchers consider that human growth hormone will create muscle mass through increased insulin-like growth factors levels that will lead to raised protein synthesis without any bad side effects while the other group of researchers claim that this fact is not proven since there were no significant studies on young healthy people.
Furthermore, the idea that human growth hormone affects muscle protein synthesis in the same way as a placebo does is supported by many research findings.
It is considered that human growth hormone may create a tissue that interconnects muscles in very short periods of time. If such effects do really exist they “may promote resistance to injury or faster repair [but] would make the muscle no more capable of force generation”. On December 13, 2007, was the release of the Mitchell Report in which was mentioned about 86 players who were detected to have used performance-improving drugs while playing in the Major Leagues. In the report there was the following statement: "Players who use Human Growth Hormone apparently believe that it assists their ability to recover from injuries and fatigue".
Other approved uses
Human growth hormone is actively used in short stature treatment but it should be noted that this applies only those problem that is not related to HGH deficiency. Results are much worse when short stature is solely attributable to deficiency of human growth hormone. Here are other reasons that cause short stature: Turner syndrome, chronic renal failure, Prader–Willi syndrome, intrauterine growth restriction, and strong idiopathic short stature. The treatment includes usage of higher doses of HGH that increases production of hormone and blood levels well above normal ("physiologic"). Side effects are very rare and do not depend on high doses, they vary somehow due to the diseases that are treated.
One version of rHGH has also been FDA approved for increasing of muscle mass that is decreased due to AIDS.
Human Growth Hormone Usage
Human Growth Hormone comes in an injectable form and may be taken subcutaneously or intramuscularly. If you decide to inject human growth hormone intramuscularly, it will have a bioavailability of nearly sixty-three percent. But when injected subcutaneously human growth hormone has bioavailability of about seventy-five percent.
You should know that the way you choose to inject HGH also influences a Somatropin hormone half-life. While administrated subcutaneously, human growth hormone carries of about 3.8 hours. But if human growth hormone is injected intramuscularly, the half-life will be approximately 4.9 hours.
You maybe think that these marks are too short for a half-life but do not be worry. Be sure the all effects will definitely surpass these numbers since IGF-1 will be significantly increased and the results will be much longer than twenty-four hours.
For therapeutic purposes, Human Growth Hormone dosages for men generally consist approximately 1-3iu per day. In rare cases a dosage administrated may constitute much as 4iu’s per day. Talking about dosages for females it should be mentioned that Human Growth Hormone doses generally consist the 1-2iu per day. Sometimes, the dose may be a bit less than 1iu per day, which may be commonly used in anti-aging programs during long periods of time.
In cases with athletes, if their goal is to improve performance, a dosage range of HGH may vary greatly. For male athletes, a dosage of 2-4iu per day is most frequent, and it may become really effective for professional athletes and for sport amateurs. Administration of a human growth hormone by athletes helps in fat loss increase and improvement of recovery and all the processes which are connected with a hormone.
It is also recommended to combine human growth hormone injections with anabolic steroids intake in order to enhance performance greatly. In such a way an anabolic steroid course becomes really more effective. For the female athletes a dose of human growth hormone for achieving the same beneficial results should constitute 1-2iu per day.
No doubts that doses mentioned above will provide remarkable results, but for truly beneficial effects during performance and muscle tissue growth increase the total dose will should be increased. For male athletes a dose should consist 6-8iu per day and during very long period of time.
Of course you may increase dosages and results also will be improved but you should take into account that the risk of unpleasant side effects will grow too. Female athletes who want to achieve truly beneficial results will need to inject the 3-4iu per day range.
You should not forget that despite the fact that you may take large doses, human growth hormone does not affect quickly. There is no sense to use human growth hormone for a short period of time. If you want to increase fat loss improve recovery period, the course should last for 8-12 weeks of usage with 16 weeks being far more productive. For remarkable anabolic results, the user will need to plan on long human growth hormone cycle at a decent dose for a minimum of six months. In fact, if it is used for therapeutic goals, specifically during anti-aging program course, total usage will be indefinite. What is more, for achieving definite results a human growth hormone therapy should last for a year or even longer.