Growth hormone

 

Growth hormone

Introduction

Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in human development. GH also stimulates production of insulin-like growth factor 1 (IGF-1) and increases the concentration of glucose and free fatty acid. It is a type of mitogen which is specific only to the receptors on certain types of cells. GH 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. 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.

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 and are closely related to human chorionic somatomammotropin (also known as placental lactogen) genes. GH, human chorionic somatomammotropin, and prolactin belong to a group of homologous hormones with growth-promoting and lactogenic activity.

Structure

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. Several molecular isoforms of GH exist in the pituitary gland and are released to blood. In particular, a variant of approximately 20 kDa originated by an alternative splicing is present in a rather constant 1:9 ratio.

Regulation

Secretion of growth hormone (GH) in the pituitary is regulated by the neurosecretory nuclei of the hypothalamus. These cells release the peptides growth hormone-releasing hormone (GHRH or somatocrinin) and growth hormone-inhibiting hormone (GHIH or somatostatin) into the hypophyseal portal venous blood surrounding the pituitary. GH release in the pituitary is primarily determined by the balance of these two peptides, which in turn is affected by many physiological stimulators (e.g., exercise, nutrition, sleep) and inhibitors (e.g., free fatty acids) of GH secretion.

Somatotropic cells in the anterior pituitary gland then synthesize and secrete GH in a pulsatile manner, in response to these stimuli by the hypothalamus. The largest and most predictable of these GH peaks occurs about an hour after onset of sleep with plasma levels of 13 to 72 ng/mL Maximal secretion of GH may occur within minutes of the onset of slow-wave (SW) sleep (stage III or IV). Otherwise 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 even 45 ng/mL. Between the peaks, basal GH levels are low, usually less than 5 ng/mL for most of the day and night.

A number of factors are known to affect GH secretion, such as age, sex, diet, exercise, stress, and other hormones. Young adolescents secrete GH at the rate of about 700 μg/day, while healthy adults secrete GH at the rate of about 400 μg/day.[20] Sleep deprivation generally suppresses GH release, particularly after early adulthood.[21]

Stimulators[quantify] of growth hormone (GH) secretion include:

·       Peptide hormones

·       GHRH (somatocrinin) through binding to the growth hormone-releasing hormone receptor (GHRHR)

·       Ghrelin through binding to growth hormone secretagogue receptors (GHSR)

·       Sex hormones

o   Increased androgen secretion during puberty (in males from testes and in females from adrenal cortex)

o   Testosterone and DHEA

o   Estrogen

·       Clonidine, moxonidine and L-DOPA by stimulating GHRH release, α4β2 nicotinic agonists, including nicotine, which also act synergistically with clonidine or moxonidine.[

·       Hypoglycemia,

·       arginine, pramipexole, ornitine, lysine, tryptophan, γ-Aminobutyric acid and propranolol by inhibiting somatostatin release

·       Deep sleep

·       Glucagon

·       Sodium oxybate or γ-Hydroxybutyric acid

·       Niacin as nicotinic acid (vitamin B3)

·       Fasting

·       Insulin

·       Vigorous exercise

Inhibitors[quantify] of GH secretion include:

·       GHIH (somatostatin) from the periventricular nucleus

·       circulating concentrations of GH and IGF-1 (negative feedback on the pituitary and hypothalamus)

·       Hyperglycemia

·       Glucocorticoids

·       Dihydrotestosterone

·       Phenothiazines

Functions

Effects of growth hormone on the tissues of the body can generally be described as anabolic (building up). Like most other peptide 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 cell membranes. Thus, GH exerts some of its effects by binding to receptors on target cells, where it activates the MAPK/ERK pathway. Through this mechanism GH directly stimulates division and multiplication of chondrocytes of cartilage.

2.       GH also stimulates, through the JAK-STAT signaling pathway, the production of insulin-like growth factor 1 (IGF-1, formerly known as somatomedin C), a hormone homologous to proinsulin.[40] 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 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 in the liver

·       Contributes to the maintenance and function of pancreatic islets

·       Stimulates the immune system

·       Increases deiodination of T4 to T3

·       Induces insulin resistance