Growth Hormone; Production, Functions and Control

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In this article, we discuss growth hormone under the following headings, Chemical Nature, Functions, Control, deficiency and excess.

Overview

Human growth hormone (hGH, somatropin) is a polypeptide hormone synthesized and secreted by the anterior pituitary gland.

It plays important metabolic roles which include stimulation of cellular uptake of amino acids and protein synthesis.

Among the many hormones and growth factors that collaborate to allow normal growth and development, growth hormone (GH) is one of the most important. GH is a pituitary-derived peptide hormone that is a major positive regulator of growth. In other words, it is a peptide hormone that stimulates growth of body tissues.

How do we define Growth?

Growth can be defined simply as an increase in size, and could result from cellular hyperplasia (increase in number), or hypertrophy (enlargement) or increased production of extracellular matrix. GH has all these effects. Indeed, the term ‘growth’ covers a variety of physiological processes.

Chemical Nature of Growth Hormone

Growth hormone is a peptide hormone made up of 191-amino acids. This important hormone is synthesized and secreted by cells called somatotrophs in the anterior pituitary. Growth hormone is species-specific (i.e. humans only respond to human GH).

It acts directly on target tissues to stimulate their growth. In addition, growth hormone can also stimulate the release of somatomedins from the liver.

Functions of Growth Hormone

GH has two main types of effect. Direct metabolic actions and indirect growth-promoting actions.

1. Direct metabolic actions of Growth Hormone

GH inhibits glucose uptake by muscle and adipose tissue, increases hepatic glucose output and reduces the sensitivity of muscle and adipose tissue to insulin. These actions are “diabetogenic”; in other words, growth hormone actions antagonize insulin and are synergizes with cortisol.

If glucose tolerance was poor in the first place, an unpleasant cycle called insulin resistance can ensue.

2. Indirect growth-promoting actions.

These are “insulin-like” effects of growth hormone. Growth hormone, like insulin, promotes growth. Growth-promoting effects of growth hormone are due to anabolic peptide formation mediated by insulin-like growth factors. These factors are called somatomedins. These peptides, specifically IGF-1, act on cells to directly stimulate cell proliferation and growth. This way, growth hormone stimulates skeletal and organ growth, increases the number and size of muscle cells, increases red blood cell mass, and stimulates chondroitin and collagen synthesis.

Somatomedins: What are they?

Somatomedins also known as insulin-like growth factors (IGFs), are a class of growth factors, that are structurally similar to insulin and have some affinity for insulin receptors.

Examples of somatomedins are IGF-I and IGF-II.

Somatomedins stimulate the growth of cartilage and the incorporation of sulphate into cartilage. GH stimulates somatomedin synthesis by the liver.

Control of Growth Hormone Production and Release

 

The hypothalamus releases a growth hormone-releasing factor called growth hormone-releasing hormone (GHRH), which stimulates GH release from the anterior pituitary. In addition, the hypothalamus releases somatostatin, which inhibits growth hormone release.

The balance between GHRH and somatostatin determines the level of GH secretion.

It is important to note that growth hormone release is episodic, not tonic. There is a clear 24-hour rhythm. Secretion is increased by sleep (stages III and IV, i.e. deep sleep – REM sleep diminishes secretion).

Levels are highest in children aged 15–19 years.

Levels are increased by a protein meal; by acute hypoglycaemia; by exercise; by acute stress; for the first few days of fasting.

A variety of neurotransmitters and drugs may also stimulate growth hormone release (e.g. β-endorphin, dopamine).

Growth hormone secretion is decreased by hyperglycaemia and by a rise in plasma FFAs.

Negative feedback: GH inhibits its own release (probably via somatomedins).

Growth Hormone Deficiency

Some individuals have been diagnosed with Growth hormone deficiency. This condition can be partial or complete. Furthermore, growth hormone deficiency can be congenital or acquired in childhood or adult life.

Growth hormone deficiency (GHD) results from inadequate production of growth hormone (GH) and can produce a variety of medical conditions depending on age.

Growth hormone deficiency in infancy and childhood result in growth failure. The failure in growth results in (dwarfism) in affected children.

Growth hormone deficiency in adulthood may have diminished lean body mass, poor bone density, and a number of physical and psychological manifestations.

Exogenous GH is in treatment of various disorders in which endogenous growth hormone is insufficient to meet the needs of the patient. Before now, the only source of exogenous GH was human cadavers. However, advances in biotechnology, have made recombinant DNA-derived GH available for general use.

Growth Hormone Excess

Excess GH production is most often caused by a tumor (adenoma) of the growth hormone producing cells of the pituitary gland.

In some cases, a lung tumour or the pancreatic tumor produces GHRH, which stimulates the somatotrophs to produce large amounts of GH.

Excess growth hormone production in children are very rare and cause excessive growth that may lead to extreme height called gigantism.

In adults, excess growth hormone causes acromegaly. The term refers to the enlargement of the distal parts of the body, including the chin, hands, feet, and nose. The enlargement is due to cartilage overgrowth, muscle hypertrophy, subcutaneous tissue enlargement, and skin thickening.

Therefore, patients with acromegaly present with protruding jaw bones, large hands and feet, a large nose, together with enlargement of soft tissues like the liver, heart, kidneys, and tongue.

Growth Factors other than Growth Hormone

Aside from growth hormone, there are many other agents that promote growth. Some of them are hormonal, while some are paracrine. They include somatomedins, insulin (esp. in the fetus), prolactin, placental lactogen, steroids, fibroblast growth factor, and nerve growth factor.

 

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