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 ****tomammotropin. 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 exist in the pituitary gland and are released to blood. In particular, a ~ 20 kDa variant originated by an alternative splicing is present in a rather constant 1:9 ratio,[3] while recently an additional variant of ~ 23-24 kDa has also been reported in post-exercise states at higher proportions.[4] This variant has not been identified, but it has been suggested to coincide with a 22 kDa glycosilated variant of 23 kDa identified in the pituitary gland.[5] Furthermore, these variants circulate partially 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).
Peptides released by neurosecretory nuclei of the hypothalamus (Growth hormone-releasing hormone/****tocrinin and Growth hormone-inhibiting hormone/****tostatin) into the hypophyseal portal venous blood surrounding the pituitary are the major controllers of GH secretion by the ****totropes. 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)[6] Stimulators of HGH secretion include:
peptide hormones
Growth hormone-releasing hormone (GHRH) through binding to the growth hormone-releasing hormone receptor (GHRHR)[7]
ghrelin through binding to growth hormone secretagogue receptors (GHSR)[8]
sex hormones[9]
increased androgen secretion during puberty (in males from testis and in females from adrenal cortex)
estrogen
clonidine and L-DOPA by stimulating GHRH release[10]
hypoglycemia, arginine[11] and propranolol by inhibiting ****tostatin release[10]
deep sleep[12]
fasting[13]
vigorous exercise [14]
Inhibitors of GH secretion include:
****tostatin from the periventricular nucleus [15]
circulating concentrations of GH and IGF-1 (negative feedback on the pituitary and hypothalamus)[2]
hyperglycemia[10]
glucocorticoids[16]
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.[17]
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.[18] The largest and most predictable of these GH peaks occurs about an hour after onset of sleep.[19] Otherwise there is wide variation between days and individuals. Nearly fifty percent of HGH secretion occurs during the third and fourth NREM sleep stages.[20] Between the peaks, basal GH levels are low, usually less than 5 ng/mL for most of the day and night.[19] 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.[21][22]
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
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 the MAPK/ERK pathway.[24] Through this mechanism GH directly stimulates division and multiplication of chondrocytes of cartilage.
GH also stimulates, through the JAK-STAT signaling pathway,[24] the production of insulin-like growth factor 1 (IGF-1, formerly known as ****tomedin C), a hormone homologous to proinsulin.[25] 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[26]
Contributes to the maintenance and function of pancreatic islets
Stimulates the immune system
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