human growth hormone

Human Growth Hormone or just simply called growth hormone (GH) affetct all parts of the body associated with growth. The sekeltal muscles and cartilage cells are especially sensitive to the levels of growth hormone. One of the most direct effects of the growth hormone is to maintain the epiphyseal plates of the long bones where growth takes place.

The growth hormone has the following functions affects skeletal growth, protein synthesis, and blood glucose concentration.

The problems associtated with excess secretation of GH include gigantism acromegaly. The problems of diminished secretion include dwarfism.

A deficiency of human growth hormone in children causes growth at a slower than normal rate during puberty. Slow epiphyseal growth results in short stature and larger than normal adipose tissue reserves. if there is no decrease in the secreation of GH toward the end of adolescense the individual will continue to grow to seven or even eight feet tall, resulting in giganitsm. when GH is overproduced after normal growth has ceased a condition called acromegaly from greek akros meaning "extremeity" and megas meaning "great or big" Althoguh the epiphyseal discs cartilages have closed, the small bones in the head, hands and feet continue to grow thickening rather than lenghtening.

Growth hormone (GH) is a protein-based peptide hormone. It stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide 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 1 produced naturally in animals, whereas the term somatropin refers to growth hormone produced by recombinant DNA technology,^[1] and is abbreviated "HGH" in humans.

Growth hormone is used as a prescription drug in medicine to treat children's growth disorders and adult growth hormone deficiency. In the United States, it is only available legally from pharmacies, by prescription from a doctor. In recent years in the United States, some doctors have started to prescribe growth hormone in GH-deficient older patients (but not on healthy people) to increase vitality. While legal, the efficacy and safety of this use for HGH has not been tested in a clinical trial. At this time, HGH is still considered a very complex hormone, and many of its functions are still unknown.^[2]

In its role as an anabolic agent, HGH has been abused by competitors in sports since the 1970s, and it has been banned by the IOC andNCAA. Traditional urine analysis could not detect doping with HGH, so the ban was unenforceable until the early 2000s when blood teststhat 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 targeted primarily HGH.^[2] This use for the drug is not approved by the FDA; GH is legally available only by prescription in the United States.

GH has been studied for use in raising livestock more efficiently in industrial agriculture and several efforts have been made to obtain governmental approval to use GH in livestock production. These uses have been controversial. In the United States, the only FDA-approved use of GH is the use of a cow-specific form of GH called bovine somatotropin for increasing milk production in dairy cows. Now retailers are permitted to label containers of milk as produced with or without bovine somatotropin.

Biological regulation

Peptides released by neurosecretory nuclei of the hypothalamus (Growth hormone-releasing hormone/somatocrinin and Growth hormone-inhibiting hormone/somatostatin) into thehypophyseal 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)^[8] Stimulators of HGH secretion include:

§ peptide hormones

§ Growth hormone-releasing hormone (GHRH) through binding to the growth hormone-releasing hormone receptor (GHRHR)^[9]

§ ghrelin through binding to growth hormone secretagogue receptors (GHSR)^[10]

§ sex hormones^[11]

§ increased androgen secretion during puberty (in males from testis and in females from adrenal cortex)

§ estrogen

§ clonidine and L-DOPA by stimulating GHRH release^[12]

§ hypoglycemia, arginine^[13] and propranolol by inhibiting somatostatin release^[12]

§ deep sleep^[14]

§ fasting^[15]

§ vigorous exercise ^[16]

Inhibitors of GH secretion include:

§ somatostatin from the periventricular nucleus ^[17]

§ circulating concentrations of GH and IGF-1 (negative feedback on the pituitary and hypothalamus)^[2]

§ hyperglycemia^[12]

§ glucocorticoids^[18]

§ 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.^[19]

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.^[2] The plasma concentration of GH during these peaks may range from 5 to even 45 ng/mL.^[20] The largest and most predictable of these GH peaks occurs about an hour after onset of sleep.^[21]Otherwise there is wide variation between days and individuals. Nearly fifty percent of HGH secretion occurs during the third and fourth NREM sleep stages.^[22] Between the peaks, basal GH levels are low, usually less than 5 ng/mL for most of the day and night.^[21] 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.^[23][24]

A number of factors are known to affect HGH secretion, such as age, gender, diet, exercise, stress, and other hormones.^[2] 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.^[25]

[edit]Normal functions of GH produced by the body

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:

1. 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 the MAPK/ERK pathway.^[26] Through this mechanism GH directly stimulates division and multiplication of chondrocytes of cartilage.

2. GH also stimulates, through the JAK-STAT signaling pathway,^[26] the production of insulin-like growth factor 1 (IGF-1, formerly known as somatomedin C), a hormone homologous to proinsulin.^[27] 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 homeostasis

§ Reduces liver uptake of glucose

§ Promotes gluconeogenesis in the liver^[28]

§ Contributes to the maintenance and function of pancreatic islets

§ Stimulates the immune system

[edit]Problems caused when the body produces too much GH

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.

[edit]Problems caused when the body produces too little GH

Main article: Growth hormone deficiency

The effects of growth hormone deficiency vary depending on the age at which they occur. In children, growth failure and short stature are the major manifestations of GH deficiency, with common causes including genetic conditions and congenital malformations. It can also cause delayed sexual maturity. In adults, deficiency is rare,^[29] with the most common cause a pituitary adenoma, and others including a continuation of a childhood problem, other structural lesions or trauma, and very rarely idiopathic GHD.

Adults with GHD present with non-specific problems including truncal obesity with a relative decrease in muscle mass and, in many instances, decreased energy and quality of life.^[29]

Diagnosis of GH deficiency involves a multiple-step diagnostic process, usually culminating in GH stimulation tests to see if the patient's pituitary gland will release a pulse of GH when provoked by various stimuli.