The human endocrine system is critical to mammalian cell-cell communication. In the endocrine system, hormones are secreted by endocrine glands into the circulatory system and adsorbed onto specific receptors, usually located distal to the site of secretion. The endocrine system is used by mammals to orchestrate a variety of different physiological processes, including metabolism, growth and maturation, circadian cycles and etc. HGH, or somatotropin, is produced in the anterior pituitary gland situated just below the hypothalamus which is itself situated just below the cerebral cortex of the brain. hGH is one of several hormones secreted by the anterior pituitary gland and, as noted above, influences the growth, regeneration and repair of cells, bones, muscles and organs throughout the body throughout life. Once released by the pituitary gland, HGH travels in the circulation and is taken up principally by the liver where it stimulates the production of IGF-1. IGF-1 is then released into the circulation where it attaches to cells in the body and like insulin, triggers the cell to produce certain responses which, with IGF-1, are those of growth, regeneration and repair. If they have too much they exhibit gigantism (acromegaly).
Growth hormone deficiency may be congenital or acquired. Low HGH levels are associated with the aging process and early onset of disease. The mechanism of hGH release has been elucidated and is considered to be under the control of growth hormone releasing hormone (GHRH) and somatostatin. Somatostatin prevents further release of hGH from the pituitary gland. It has been postulated that one of the key factors in aging is an imbalance in the levels of GHRH and somatostatin in the combined GHRH/Somatostatin secretion, with an increased action or effectiveness of Somatostatin over GHRH. This leads to an effective reduction in release of the stored hGH from the anterior pituitary gland. Production of growth hormone peaks at adolescence when accelerated growth is occurring and if growing children are deficient in human growth hormone, they remain as pituitary dwarfs. Daily growth hormone secretion diminishes with age with roughly half the levels at age forty that we had when we were twenty, and about one-third of those youthful levels at age sixty. In some sixty-year olds the levels are as low as 25% of the hGH levels in a twenty-year old. Symptoms of aging include loss of muscle, increase of fat, decreased physical mobility, decreased energy levels and as a result, diminished socialization, diminished healing ability and an increased risk of cardiovascular disease and decreased life expectancy.
Deficiency in growth hormone production results in a variety of medical disorders. Pathologic states found in growth hormone deficiency patients include increased cardiovascular mortality, reduced exercise capacity, reduced muscle strength, subnormal kidney function, defective sweat and temperature regulation, reduced energy expenditure and basal metabolic rate, abnormal thyroid hormone metabolism, increased fat mass, decreased lean body mass, upper body obesity and reduced bone mineral content. In children, it causes dwarfism. Most children with significant short stature do not have growth hormone (GH) deficiency as classically defined by the GH response to provocative stimuli. In adults, the consequences of acquired GH deficiency include profound reduction in lean body mass and concomitant increase in total body fat, particularly in the truncal region. Decreased skeletal and cardiac muscle mass and muscle strength lead to a significant reduction in exercise capacity. Bone density is also reduced. Adult patients with unsubstituted growth hormone deficiency often complain of general fatigue, lack of concentration and memory disabilities. The fatigue reduces their overall working capacity with negative consequences for the patients' career and daily activities. All of these GH deficiency conditions can be partially corrected by expensive GH replacement therapy with synthetic human growth hormone deficiency. Most of the aforementioned abnormalities also are present in elderly adults who, incidentally, also have very low levels of GH secretion. Administration of exogenous GH has been shown to reverse many of these metabolic changes. Additional benefits of therapy have included reduction in LDL cholesterol and improved psychological well-being. Clinical trials with elderly subjects have shown the beneficial effects of GH replacement therapy. As the growth hormone, recombinant products are currently used in general. Growth hormone cannot be given orally because it is a protein.
Most GH deficiencies are caused by defects in growth hormone release, not primary defects in the pituitary synthesis of GH. Therefore, an alternative strategy for normalizing growth hormone levels is by stimulating its release from somatotrophs. Increasing growth hormone secretion can also be achieved by stimulating or inhibiting various neurotransmitter systems in the brain and hypothalamus. As a result, the development of synthetic growth hormone-releasing agents to stimulate pituitary GH secretion are being developed, and may have several advantages over expensive and inconvenient growth hormone replacement therapy. Various ways are known to release growth hormone. Physiologic and pharmacologic stimulators of growth hormone secretion include arginine, L-dopa, glucagon, vasopressin, and insulin induced hypoglycemia, as well as activities such as sleep and exercise, indirectly cause growth hormone to be released from the pituitary by acting in some fashion on the hypothalamus perhaps either to decrease somatostatin secretion or to increase the secretion of the known secretagogue growth hormone releasing factor (GHRF) or an unknown endogenous growth hormone-releasing hormone or all of these.
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