Human growth hormone (HGH)
Human growth hormone (hGH) is a straight chain polypeptide that is secreted from the anterior pituitary gland and is present in the blood as a monomer. This hormone is essential for growth and development (bone growth, protein synthesis and cellular proliferation) and its secretion is regulated by somatostatin and hGH releasing hormone (GHRH). In acromegaly or pituitary gigantism, the level of hGH is high and most cases are caused by excessive hGH secretion due to hGH-producing adenoma. On the other hand, the level of hGH is generally low in hypopituitarism.
HGH: Growth hormone, also known as somatotropin or somatropin, is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. It is a type of mitogen which is specific only to certain kinds of cells. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by somatotropic cells within the lateral wings of the anterior pituitary gland.
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“Growth hormone (HGH) or somatotropin is a polypeptide hormone made up of 191 amino acids and has a molecular weight of 21,500 daltons. It is synthesized and secreted by the anterior pituitary gland. HGH promotes growth in soft tissue, cartilage and bones, aids protein synthesis and greatly influences the metabolism of carbohydrates and lipids.
The half life of circulating human growth hormone is relatively short (20-30 minutes). The release of HGH from the pituitary is influenced by a variety of factors including chemical stimuli and the balance between growth hormone releasing factor (GHRF) and somatostatin (growth hormone release inhibiting hormone). Sleep, stress, exercise, fasting, high protein meals, hypoglycemia and certain amino acids such as L-dopa, glucagon, arginine and histamine all cause increases in HGH secretion. HGH release is inhibited by glucose, cortisol, free fatty acids and circulating HGH.
Hypersecretion can be caused by pituitary hyperplasia or tumors or by secondary factors such as a lack of release inhibiting factors. 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.
The effect of hypersecretion of growth hormone depends on the age of the patient. In children, hypersecretion causes the phenomenon of accelerated growth with weakened bones and muscles termed gigantism. Prolonged GH excess thickens the bones of the jaw, fingers and toes. Resulting heaviness of the jaw and increased thickness of digits is referred to as acromegaly. Accompanying problems can include pressure on nerves (e.g., carpal tunnel syndrome), muscle weakness, insulin resistance or even a rare form of type 2 diabetes, and reduced sexual function.
Deficiency of GH produces significantly different problems at various ages. In children, growth failure and short stature are the major manifestations of GH deficiency. In adults the effects of deficiency are more subtle, and may include deficiencies of strength, energy, and bone mass, as well as increased cardiovascular risk.
Measurement of Growth hormone
Measuring random growth hormone is not usually meaningful. Screening tests for HGH deficiency, HGH hypersecretion and assessment of pituitary-hypothalamic function, utilize a variety of provocative tests (challenge tests). 1
The diagnosis and treatment of GH deficiency (GHD) during childhood and adolescence:
In a child with clinical criteria for GHD, a peak GH concentration below 10 µg/L , after growth hormone provocation test, has traditionally been used to support the diagnosis. A limited number of provocative agents should be used after an overnight fast in a well standardized protocol. These include arginine, clonidine, glucagon, insulin, and L-dopa.2
The diagnosis and treatment of GH deficiency (GHD) of adults:
The diagnosis of adult GH deficiency is established by provocative testing of GH secretion. Patients should be receiving stable and adequate hormone replacement for other hormonal deficits before testing. At present, the insulin tolerance test is the diagnostic test of choice. Provided adequate hypoglycemia is achieved, this test distinguishes GH deficiency from the reduced GH secretion that accompanies normal aging and obesity. The insulin tolerance test should be performed in experienced endocrine units where the test is performed frequently. The test is contraindicated in patients with electrocardiographic evidence or history of ischemic heart disease or in patients with seizure disorders. Given these precautions, the insulin tolerance test is safe; however, there is less experience in patients over the age of 60 yr.
Most normal subjects respond to insulin-induced hypoglycemia with a peak GH concentration of more than 5 µg/L. Severe GH deficiency is defined by a peak GH response to hypoglycemia of less than 3 µg/L. 3
The diagnosis and treatment of GH deficiency (GHD) of adolescents in the transition to adults:
The diagnosis of adult GH deficiency of adolescents in the transition to adults is established by GH measurement in response to an Insulin tolerance test (ITT). Severe GHD in adults has been defined as a peak GH response <3 µg/l in response to an ITT and is an accepted criterion for GH replacement therapy in adults. However, this definition is likely to be too conservative in the transition period. In normal children, the most exuberant GH response to a stimulation test occurs in late puberty with GH levels inevitably exceeding 5 µg/l. So the proposed criteria for severe GHD in the transition period should be <5 µg/l in response to a GH stimulation test; 4
1. Biochemical Assessment and Long-Term Monitoring in Patients with Acromegaly: Statement from a Joint Consensus Conference of The Growth Hormone Research Society and The Pituitary Society. The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 7 3099-3102
2. Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. GH Research Society. J Clin Endocrinol Metab. 2000 Nov;85(11):3988-9.
3.Consensus Guidelines for the Diagnosis and Treatment of Adults with Growth Hormone Deficiency: Summary Statement of the Growth Hormone Research Society Workshop on Adult Growth Hormone Deficiency
The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 2 379-381
4. Consensus statement on the management of the GH-treated adolescent in the transition to adult care, European Journal of Endocrinology, Vol 152, Issue 2, 165-170.”
GH is a stress hormone that raises glucose and free fatty acids. It stimulates IGF which raises proteins.
GH 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.
In its role as an anabolic agent, HGH has been abused by competitors in sports at least since 1982, 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 targeted primarily HGH. This use for the drug is not approved by the FDA.
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.
Cortisol
Cortisol, known more formally as hydrocortisone (INN, USAN, BAN), is a steroid hormone, to be more specific a glucocorticoid, produced by the zona fasciculata of the adrenal cortex. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat, protein and carbohydrate metabolism. It also decreases bone formation. Various synthetic forms of cortisol are used to treat a variety of diseases
Production and release
Cortisol is produced in the human body by the adrenal gland in the zona fasciculata,the second of three layers comprising the adrenal cortex. The cortex forms the outer "bark" of each adrenal gland, situated atop the kidneys. The release of cortisol is controlled by the hypothalamus, a part of the brain. The secretion of corticotropin-releasing hormone (CRH) by the hypothalamus triggers cells in the neighboring anterior pituitary to secrete another hormone, adrenocorticotropic hormone (ACTH), into the vascular system, through which blood carries it to the adrenal cortex.
Main functions in the body
In the fasting state, cortisol stimulates gluconeogenesis (formation, in the liver, of glucose from certain amino acids, glycerol, lactate, and/or propionate), and it activates anti-stress[citation needed] and anti-inflammatory pathways.
It downregulates the Interleukin-2 receptor (IL-2R) on "Helper" (CD4+) T-cells. This results in the inability of Interleukin-2 to upregulate the Th2 (Humoral) immune response and results in a Th1 (Cellular) immune dominance. This results in a decrease in B-cell antibody production. Cortisol prevents the release of substances in the body that cause inflammation. This is why cortisol is used to treat conditions resulting from overactivity of the B-cell-mediated antibody response such as inflammatory and rheumatoid diseases, and allergies. Low-potency hydrocortisone, available over the counter in some countries, is used to treat skin problems such as rashes, eczema, and others.
Cortisol plays an important role in glycogenolysis, the breaking down of glycogen to glucose-1-phosphate and glucose, in liver and muscle tissue. Glycogenolysis is stimulated by epinephrine and/or norepinephrine, however cortisol facilitates the activation of glycogen phosphorylase, which is essential for the effects of epinephrine on glycogenolysis.
Elevated levels of cortisol, if prolonged, can lead to proteolysis and muscle wasting.
Several studies have shown a lipolytic (breakdown of fat) effect of cortisol, although, under some conditions, cortisol may somewhat suppress lipolysis.
Another function is to decrease bone formation.
ACTH
ACTH is produced in the pituitary and the main biological function is to increase the synthesis and release of all adrenal steroid hormones. ACTH secretion is in turn controlled by the hypothalamic hormone – corticotropin releasing hormone (CRH) and by negative feedback from cortisol.
Parathyroid hormone (PTH)
Parathyroid hormone (PTH) raises blood ionized calcium levels by promoting bone resorption and releasing calcium and phosphate from the bone to the extracellular fluid through direct action on bone. PTH also promotes reabsorption of ionized calcium and inhibit the renal reabsorption of phosphate through the action on renal tubular. PTH is rapidly metabolized in the liver and kidney to primarily biological active N-terminal and biological inactive C-terminal fragment with much longer half lives. Intact PTH or wPTH assays accurately reflect PTH-secretion kinetics because of being less influenced by the declining renal function. Therefore, intact PTH is a valuable marker to find the diseases of the parathyroid gland and the kidney to judge success or failure of operation removing malignant parathyroid gland and to observe post-operative recovery.
