Growth hormone

A recombinant form of hGH called somatropin (INN) is used as a prescription drug to treat children’s growth disorders and adult growth hormone deficiency.

Use of the drug for performance enhancement is not currently approved by the FDA.

THE only FDA-approved use of GH for livestock is the use of bovine somatotropin for increasing milk production in dairy cows.

Hormone extracted from human cadavers is abbreviated hGH.

The main growth hormone produced by recombinant DNA technology has the generic name somatropin

Genes for human growth hormone, known as growth hormone 1 (somatotropin; pituitary growth hormone) and growth hormone 2 (placental growth hormone; growth hormone variant), are localized in the q22-24 region of chromosome 17.

Secretion of growth hormone in the pituitary is regulated by the neurosecretory nuclei of the hypothalamus.

Growth hormone-releasing hormone and somatostatin traverse hypothalamic-pituitary portal system to induce or suppress growth hormone production, respectively,by signaling specific somatotroph cell surface G protein coupled receptors.

These cells release the peptides Growth hormone-releasing hormone and Growth hormone-inhibiting hormone into the hypophyseal portal venous blood surrounding the pituitary.

GH release in the pituitary is determined by the balance of these two peptides, which in turn is affected by many physiological stimulators, such as exercise, nutrition, and sleep.

Growth hormone nadir occurs mainly during the daytime when levels are most undetectable, especially in the elderly or obese.

Insulin induced hyperglycemia promotes growth hormone release within 45 minutes, during the induced glucose trough.

Amino acids arginine and losing administered intravenously induce growth hormone secretion.

Women have disorderly growth hormone release compared to men with more growth hormone secreted per pulse, higher basal growth hormone levels, and more growth hormone resistance than men.

Growth hormone circulating half life is about 14 minutes.

Growth hormone production peaks during mid adolescence, levels decline after growth ceases, and remains stable until adulthood when it wanes with aging by about 14% per decade, most likely due to decreased output of GHRH.

Somatotropic cells in the anterior pituitary gland synthesize and secrete GH in a pulsatile manner, in response to these stimuli by the hypothalamus.

Growth hormone release is augmented by exercise and blunted by normal aging and adiposity.

Factors known to affect GH secretion, such as age, sex, diet, exercise, stress, and other hormones.

GH peaks occurs about an hour after onset of sleep with plasma levels of 13 to 72 ng/mL.

For each unit increase in BMI, the secretion of growth hormone drops by 6%.

Levels of circulating growth hormone, and the degree of adosity, as well as the IGF-1 receptor, determine the transduction growth hormone signal and tissue specific responses to growth hormone receptor activation.

Chondrocyte proliferation and childhood linear growth require both growth hormone and IGF-1.

Growth hormone release is suppressed by glucose loading and stimulated by insulin induced hypoglycemia.

Glucose loading suppresses serum growth hormone to less than 0.7 mcg per liter in women and to less than .07 mcg per liter in men.

Malnutrition or hypoglycemia leads to increase growth hormone levels.

There is wide variation between days and individuals.

Nearly fifty percent of GH secretion occurs during the third and fourth NREM sleep stages.

Surges of secretion during the day occur at 3- to 5-hour intervals.

The plasma concentration of GH during these peaks may range from 5 to 45 ng/mL.

Between the peaks, basal GH levels are low, usually less than 5 ng/mL for most of the day and night.

Young adolescents secrete GH at the rate of about 700 ?g/day.

Adults secrete GH at the rate of about 400 Micrograms per day.

Sleep deprivation generally suppresses GH release.

Sleep deprivation suppresses growth hormone release, particularly after early adulthood.

Stimulators of growth hormone (GH) secretion include:

peptide hormones

GHRH by binding to the growth hormone-releasing hormone receptor.

Gastric ghrelin by binding to growth hormone secretagogue receptors (GHSR).

sex hormones.

increased androgen secretion during puberty from testes inmates and in females from the adrenal cortex in females.

estrogen

clonidine and L-DOPA by stimulating GHRH release

nicotine, which also act synergistically with clonidine.

hypoglycemia, arginine and propranolol by inhibiting somatostatin release.

deep sleep

niacin as nicotinic acid (Vitamin B3)

fasting

vigorous exercise

Inhibitors of GH secretion include:

GHIH (somatostatin) from the periventricular nucleus

circulating concentrations of GH and IGF-1

hyperglycemia

glucocorticoids

dihydrotestosterone

Insulin-like growth factor1 , the peripheral target of growth hormone, suppresses growth hormone by exerting negative feedback and regulates paracrine growth hormone receptor trafficking.

Neurotransmitters, and amino acids modulate hypothalamus release and actions of GHRH, somatostatin, or both, with pulsatile growth hormone secretory patterns determined by age, nutritional status, and gender.

Pulses of growth hormone occur mainly nocturnally, and account for most of the daily growth hormone production, and 85% or greater.

Effects of growth hormone on the tissues of the body are anabolic.

GH acts by interacting with a specific receptors on the surface of cells.

The Increase in height during childhood is the most widely known effect.

GH binds to receptors on target cells, where it activates the MAPK/ERK pathway stimulating division and multiplication of chondrocytes of cartilage.

GH stimulates, through the JAK-STAT signaling pathway, the production of insulin-like growth factor 1 (IGF-1) a hormone homologous to proinsulin.

Other effects on the body of growth hormone include:

Increases calcium retention, and strengthens and increases the mineralization of bone.

Increases muscle mass through sarcomere hypertrophy.

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

Contributes to the maintenance and function of pancreatic islet cells

Stimulates the immune system

Increases deiodination of T4 to T3

GH is required for linear growth during childhood, but metabolic functions unrelated to growth are maintained by growth hormone throughout adulthood and include: anabolic effects, antagonism of insulin action, decreases adipocyte glucose uptake, while increasing hepatic glucose production.

GH directs amino acids toward muscle protein synthesis and induces lipolysis, with the loss of visceral adipose tissue, and release of free fatty acids, as well as lowering of cholesterol and apolipoprotein B levels, with increased high-density lipoprotein levels.

GH enables lipolysis in the fasting state conferring homeostatic energy metabolism.

GH induces osteoblastic differentiation and proliferation in bone formation, dampens osteoclast activation, increases renal sodium absorption.

Growth hormone excess is most commonly associated with an anterior pituitary tumor composed of somatotroph cells.

Somatotroph adenomas are benign and grow slowly, but lead to gigantism and acromegaly.

Surgical removal of the pituitary tumor is the usual treatment for GH-producing tumors.

Radiation or a GH antagonist such as pegvisomant may be employed to shrink the tumor or block its function.

Octreotide and bromocriptine can be used to block GH secretion because both somatostatin and dopamine negatively inhibit GHRH-mediated GH release from the anterior pituitary.

Growth hormone deficiency effects vary depending on the age at which they occur.

Suppression of growth hormone production in adults may be caused by structural damage, such as an expanding intracellular mass compressing somatotropin function, a damaged hypothalamic pituitary neuroendocrine pathway, or local vascular compromise from surgery, radiation, or head trauma.

Survivors of childhood cancers are the risk of developing growth hormone deficiency in adulthood, especially if they have received prior radiation to the head or neck.

Patient with normal pituitary function age  adjusted growth hormone levels are invariably within normal limits.

Manifestations of GH deficiency in children are growth failure, the development of a short stature, and delayed sexual maturity.

In adults, growth hormone alteration contributes to increased osteoclast activity, resulting in osteoporosis.

Growth hormone deficiency is rare in adults, with the most common cause being a pituitary adenoma.

Growth hormone deficiency in adults may related to a continuation of a childhood problem, other structural lesions or trauma, and very rarely idiopathic GHD.

Adults with GHD have a relative increase in fat mass and a relative decrease in muscle mass and, in many instances, decreased energy and quality of life.

Diagnosis of GH deficiency involves GH stimulation tests to see if the patient’s pituitary gland will release a pulse of GH when provoked by various stimuli.

GH has a mental and emotional well-being and maintaining a high energy level.

Adults with GH deficiency often have higher rates of depression.

Improves cognitive function in the treatment of patients with cognitive impairment that is a result of GH deficiency.

Treatment with exogenous GH is indicated only in limited circumstances: replacement therapy in adults with GH deficiency of either childhood-onset or adult-onset, usually as a result of an acquired pituitary tumor.

With GH deficiency use of exogenous GH reduces fat mass, increases lean mass, increases bone density, improves lipid profile, reduces cardiovascular risk factors, and improves psychosocial well-being.

Can be used to treat conditions that produce short stature but are not related to deficiencies in GH, the results are not as dramatic when compared to short stature that is solely attributable to deficiency of GH.

Causes of shortness often treated with GH are Turner syndrome, chronic renal failure, Prader-Willi syndrome, intrauterine growth restriction, and severe idiopathic short stature.

Higher doses of growth hormone are required to produce significant acceleration of growth in these conditions.

GH in healthy elderly patients increased muscle by about 2 kg and decreased body fat by the same amount, but no other critical factors were affected, such as bone density, cholesterol levels, lipid measurements, maximal oxygen consumption, or any other factor that would indicate increased fitness.

In the above Stanford study, no gain in muscle strength was noted suggesting GH merely let the body store more water in the muscles rather than increase muscle growth.

FDA classifies anabolic steroids as controlled substances

Side-effects: Injection-site reaction is common, rarely, patients can experience joint swelling, joint pain, carpal tunnel syndrome, and an increased risk of diabetes.

May also be a risk factor for Hodgkin’s lymphoma.

Studies have not been able to support claims that human growth hormone can improve the athletic performance of professional male athletes.

it is legal to give a bovine GH to dairy cows to increase milk production, and is legal to use GH in raising cows for beef;, but its use in poultry farming is illegal in the United States.

Biosynthetic human growth hormone replaced pituitary-derived human growth hormone for therapeutic use.

Creutzfeldt-Jakob disease presumably caused by infectious prions were found in individuals that had received cadaver-derived HGH, ten to fifteen years previously.

Action mediated by growth hormone receptor which is expressed primarily in the liver and cartilage and is composed of preformed dimers which undergo alteration when occupied by a growth hormone ligand that promotes signaling.

Cleavage of growth hormone receptor yields a circulating growth hormone binding protein, which prolongs the half-life and mediates cell transport of growth hormone.

The pituitary receives stimulatory and inhibitory effects via the hypothalamus.

Secretion is reduced in patients with HIV infection and abdominal fat accumulation and relative growth hormone deficiency is seen in one third of such patients.

Relative deficiency common among patients with HIV and lipodystrophy and is seen mostly in men with HIV and abdominal fat accumulation.

People being treated for too much growth hormone may develop gallstones.

GH production can be suppressed by structural damage such as in expanding intracellular mass, damaged hypothalamic pituitary neuroendocrine pathways, or local vascular compromise from surgery, radiation, or head trauma.

Survivors of childhood cancers are at risk for developing GH deficiency in adulthood, especially if they receive radiation to the head or neck.

Adult growth hormone deficiency is associated with central obesity, loss of lean muscle mass, decreased bone mass and impaired quality of life.

Adult growth hormone deficiency is associated with increased fat mass, increased cholesterol, increased low density lipoproteins, increased triglycerides, and apolipoprotein B,  and lean body mass is decreased.

Growth hormone antagonizes insulin action, adult growth hormone deficiency may be associated with diabetes which is probably aggravated by central obesity.