Human Growth
Growth hormone ( GH ) is a protein-based poly-peptide hormone. It stimulates growth and cell reproduction and regeneration in humans and other animals. It is a 191-amino acid, single-chain polypeptide hormone that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior pituitary gland. Somatotropin refers to the growth hormone produced natively and naturally in animals, whereas the term somatropin refers to growth hormone produced by recombinant DNA technology, and is abbreviated "rhGH" in humans.
Growth hormone is used clinically to treat children's growth disorders and adult growth hormone deficiency. In recent years, replacement therapies with human growth hormones (hGH) have become popular in the battle against aging and weight management. Reported effects on GH deficient patients (but not on healthy people) include decreased body fat, increased muscle mass, increased bone density, increased energy levels, improved skin tone and texture, increased sexual function and improved immune system function. At this time hGH is still considered a very complex hormone and many of its functions are still unknown.
In its role as an anabolic agent, HGH has been used by competitors in sports since the 1970s, and it has been banned by the IOC and NCAA. Traditional urine analysis could not detect doping with hGH, so the ban was unenforceable until the early 2000s, when blood tests that could distinguish between natural and artificial hGH were starting to be developed. Blood tests conducted by WADA at the 2004 Olympic Games in Athens, Greece primarily targeted hGH.
Gene locus
Main articles: Growth hormone 1 and Growth hormone 2Genes for human growth hormone, known as growth hormone 1 (somatotropin) and growth hormone 2, are localized in the q22-24 region of chromosome 17 and are closely related to human chorionic somatomammotropin (also known as placental lactogen) genes. GH, human chorionic somatomammotropin, and prolactin (PRL) are a group of homologous hormones with growth-promoting and lactogenic activity.
Structure
The major isoform of the human growth hormone is a protein of 191 amino acids and a molecular weight of 22,124 daltons. The structure includes four helices necessary for functional interaction with the GH receptor. It appears that, in structure, GH is 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.
Several molecular isoforms of GH circulate in the plasma. A percentage of the growth hormone in the circulation is bound to a protein (growth hormone-binding protein, GHBP) which is the truncated part of the growth hormone receptor, and an acid labile subunit (ALS).
Regulation
Peptides released by neurosecretory nuclei of the hypothalamus (Growth hormone-releasing hormone and somatostatin) into the portal venous blood surrounding the pituitary are the major controllers of GH secretion by the somatotropes. However, although the balance of these stimulating and inhibiting peptides determines GH release, this balance is affected by many physiological stimulators (e.g., exercise, nutrition, sleep) and inhibitors of GH secretion (e.g., Free fatty acids)
Stimulators of GH secretion include:
-
peptide hormones
- Growth hormone releasing hormone (GHRH also known as somatocrinin) through binding to the growth hormone releasing hormone receptor (GHRHR)
- ghrelin through binding to growth hormone secretagogue receptors (GHSR)
-
sex hormones
- increased androgen secretion during puberty (in males from testis and in females from adrenal cortex)
- estrogen
- clonidine and L-DOPA by stimulating GHRH release
- hypoglycaemia, arginine and propranolol by inhibiting somatostatin release
- deep sleep
- fasting
- vigorous exercise
Inhibitors of GH secretion include:
- somatostatin from the periventricular nucleus
- circulating concentrations of GH and IGF-1 (negative feedback on the pituitary and hypothalamus)
- hyperglycemia
- glucocorticoids
- dihydrotestosterone
In addition to control by endogenous and stimulus processes, a number of foreign compounds (xenobiotics such as drugs and endocrine disruptors) are known to influence GH secretion and function.
Secretion patterns
HGH is synthesized and secreted from the anterior pituitary gland in a pulsatile manner throughout the day; surges of secretion occur at 3- to 5-hour intervals. The plasma concentration of GH during these peaks may range from 5 to even 45 ng/mL. 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. Nearly fifty percent of HGH secretion occurs during the third and fourth REM sleep stages. Between the peaks, basal GH levels are low, usually less than 5 ng/mL for most of the day and night. Additional analysis of the pulsatile profile of GH described in all cases less than 1 ng/ml for basal levels while maximum peaks were situated around 10-20 ng/mL.
A number of factors are known to affect HGH secretion, such as age, gender, diet, exercise, stress, and other hormones. Young adolescents secrete HGH at the rate of about 700 μg/day, while healthy adults secrete HGH at the rate of about 400 μg/day.
Functions of GH
Effects of growth hormone on the tissues of the body can generally be described as anabolic (building up). Like most other protein hormones, GH acts by interacting with a specific receptor on the surface of cells.
Increased height during childhood is the most widely known effect of GH. Height appears to be stimulated by at least two mechanisms:
- Because polypeptide hormones are not fat-soluble, they cannot penetrate sarcolemma. Thus, GH exerts some of its effects by binding to receptors on target cells, where it activates a second messenger. Through this mechanism GH directly stimulates division and multiplication of chondrocytes of cartilage.
- GH also stimulates production of insulin-like growth factor 1 (IGF-1, formerly known as somatomedin C), a hormone homologous to proinsulin. The liver is a major target organ of GH for this process and is the principal site of IGF-1 production. IGF-1 has growth-stimulating effects on a wide variety of tissues. Additional IGF-1 is generated within target tissues, making it what appears to be both an endocrine and an autocrine/paracrine hormone. IGF-1 also has stimulatory effects on osteoblast and chondrocyte activity to promote bone growth.
In addition to increasing height in children and adolescents, growth hormone has many other effects on the body:
- Increases calcium retention, and strengthens and increases the mineralization of bone
- Increases muscle mass through sarcomere hyperplasia
- Promotes lipolysis
- Increases protein synthesis
- Stimulates the growth of all internal organs excluding the brain
- Plays a role in fuel homeostasis
- Reduces liver uptake of glucose
- Promotes gluconeogenesis in the liver
- Contributes to the maintenance and function of pancreatic islets
- Stimulates the immune system
Excesses
The most common disease of GH excess is a pituitary tumor composed of somatotroph cells of the anterior pituitary. These somatotroph adenomas are benign and grow slowly, gradually producing more and more GH. For years, the principal clinical problems are those of GH excess. Eventually the adenoma may become large enough to cause headaches, impair vision by pressure on the optic nerves, or cause deficiency of other pituitary hormones by displacement.
Prolonged GH excess thickens the bones of the jaw, fingers and toes. Resulting heaviness of the jaw and increased size of digits is referred to as acromegaly. Accompanying problems can include sweating, pressure on nerves (e.g., carpal tunnel syndrome), muscle weakness, excess sex hormone binding globulin (SHBG), insulin resistance or even a rare form of type 2 diabetes, and reduced sexual function.
GH-secreting tumors are typically recognized in the fifth decade of life. It is extremely rare for such a tumor to occur in childhood, but, when it does, the excessive GH can cause excessive growth, traditionally referred to as pituitary gigantism.
Surgical removal is the usual treatment for GH-producing tumors. In some circumstances, focused radiation or a GH antagonist such as pegvisomant may be employed to shrink the tumor or block function. Other drugs like octreotide (somatostatin agonist) and bromocriptine (dopamine agonist) can be used to block GH secretion because both somatostatin and dopamine negatively inhibit GHRH-mediated GH release from the anterior pituitary.
Deficiencies
Main article: Growth hormone deficiencyThe effects of growth hormone deficiency vary depending on the age at which they occur. In children, growth failure and short stature are the major manifes
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Growth hormone (GH) is a protein-based poly-peptide hormone. It stimulates growth and cell reproduction and regeneration in humans and other animals.
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