Hormonal communication

Endocrine system - A communication system using hormones as signalling molecules.

Hormones - Molecules ( proteins or steroid) that are released by endocrine glands directly into the blood. They act as messenger, carrying a signal from the endocrine gland to a specific target organ or tissue.

Target cells - For non steroid hormones, cells that posses a specific receptor on their plasma ( cell surface) membrane. The shape of the receptor is complimentary to the shape of the hormone molecule. Many similar cells together form a target tissue.

• The endocrine system is another system, in addition to the nervous system, used for communication around the body.

• The endocrine system uses the blood circulatory system to transport its signals.

• The signals released by the endocrine system are molecules called hormones.

• The blood system transports materials all over the body; therefore any hormone released into the blood will be transported throughout the body. 

There are two types of hormone:

• Protein and peptide hormones ( e.g., adrenaline, insulin and glucagon)
• Steroid hormones (e.g. oestrogen and testosterone)

These two types of hormones work in different ways.

Proteins are not soluble in the phospholipid membrane and do not enter the cell. Protein hormones need to bind to the cell surface membrane and release a secondary messenger into the cell.

Steroid hormones can pass through the membrane and enter the cell and the nucleus, to have a direct effect on the DNA in the nucleus.

• Hormones are released directly into the blood from endocrine glands.

• The endocrine glands are ductless glands- they consist of groups of cells that manufacture and release the hormone directly into the blood in capillaries running through the gland.

• Endocrine glands have groups of cells with associated capillaries but no visible ducts.

• Hormones always have a specific function- they are transported all over the body, but they have an effect in only one type of tissue.

• The cells receiving an endocrine signal are called target cells. These cells may be grouped together in a target tissue.

• Alternatively, they may be more widely dispersed in a number of target cells ( e.g., adrenaline has many target tissues).

• For non-steroid hormones, the target cells must possess a specific receptor on their plasma membrane that is complementary in shape to the shape of the signalling molecule (hormone). The hormone binds to this receptor and initiates changes in the cell.

• If all the cells in the body possess such a receptor then all the cells can respond to the signal. However, each hormone is different from all the others. This means that a hormone can be carried in the blood without affecting cells that don't possess the specific receptors. Only those specific target cells that possess the correct receptor will respond to the hormone.

• Non-steroid hormones are known as first messengers. They are signaling molecules outside the cell that bind to the cell surface membrane and initiate an effect inside the cell. This effect is usually releasing another signaling molecule called the second messenger.

• The second messenger stimulates a change in the activity of the cell.

• Many non-steroid hormones act via a G protein in the membrane. The G protein is activated when the hormone binds with the receptor. The G protein, in turn, activates an effector molecule (usually an enzyme that converts an inactive molecule into the active second messenger).

• In many cells, the effector molecule is the enzyme adenyl cyclase, which converts ATP to cAMP. cAMP is the second messenger. This second messenger can act directly on another protein or it may initiate a cascade of enzyme-controlled reactions that alter the activity of the cell.

Adrenal cortex- The outer layer of the adrenal gland.

Adrenal gland- One of a pair of glands lying above the kidneys, which releases adrenaline and a number of other hormones known as corticoids ( or corticosteroids) such as aldosterone.

Adrenaline- A hormone released from the adrenal glands, which stimulates the body to prepare for fight or flight.

Adrenal medulla- The inner layer of the adrenal gland.

• The adrenal glands are endocrine glands.

• They are found lying just above the kidneys - one on either side of the body.

• Each gland is divided into the outer adrenal cortex and the inner adrenal medulla.

• Both regions are well supplied with blood vessels and produce hormones which are secreted directly into blood vessels.

The adrenal gland has an outer capsule surrounding three distinct layers of cells, which are the:

• Zona glomerulosa - the outermost layer which secretes mineralocorticoids such as aldosterone.
• Zona fasciculata- the middle layer, which secretes glucocorticoids such as cortisol.
• Zona reticularis- the innermost layer, which is thought to secrete precursor molecules that are used to make sex hormones.

The adrenal medulla is found at the center of the adrenal gland and secretes adrenaline and noradrenaline.

• The adrenal cortex uses cholesterol to produce a range of hormones.

• These hormones are steroid-based and are able to enter cells directly by dissolving into the cell surface membrane.

• The steroid hormones enter the nucleus and have a direct effect on the DNA to cause protein synthesis.

• The steroid hormone passes through the cell membrane of the target cell.

• The steroid hormone binds with a specific receptor (with a complementary shape) in the cytoplasm.

• The receptor-steroid hormone complex enters the nucleus of the target cell and binds to another specific receptor on the chromosomal material.

• Binding stimulates the production of messenger RNA (mRNA) molecules, which code for the production of proteins.

• Mineralocorticoids from the zona glomerulosa help to control the concentrations of sodium and potassium in the blood. As a result, they also contribute to maintaining blood pressure. Aldosterone acts on the cells of the distal tubules and collecting ducts in the kidney. It increases absorption of sodium ions, decreases absorption of potassium ions, and increases water retention so increasing blood pressure.

• Glucocorticoids (e.g. cortisol) from the zona fasciculata help to control the metabolism of carbohydrates, fats, and proteins in the liver. Cortisol is released in response to stress or as a result of low blood glucose concentration. It stimulates the production of glucose from stored compounds (especially glycogen, fats, and proteins) in the liver.

• Cortisol may also be released by the zona reticularis. However, if the correct enzymes are not present for the release of cortisol, then the zona reticularis releases precursor androgens into the blood. These are taken up by the ovaries or testes and converted to sex hormones. The sex hormones help the development of the secondary sexual characteristics and regulate the production of gametes.

• Adrenaline is released from the adrenal medulla into the blood and is transported throughout the body.

• Adrenaline is a polar molecule derived from the amino acid tyrosine, therefore it cant enter cells through the plasma membrane, like steroid hormones.

• Therefore, it must be detected by specialized receptors on the plasma membrane of the target cells.

• Many cells have adrenaline receptors so the effects are widespread.

• The role of adrenaline is to prepare the body for activity, which it does in a number of ways.

• Relaxing smooth muscle in the bronchioles.

• Increasing stroke volume of the heart.

• Increasing heart rate.

• Causing general vasoconstriction to raise blood pressure.

• Stimulating conversion of glycogen to glucose.

• Dilating the pupils.

• Increasing mental awareness.

• Inhibiting the action of the gut.

• Causing body hair to stand erect.

The pancreas is a small organ lying just below the stomach. It can perform both endocrine and exocrine functions. The two main secretions of the pancreas are:

• Pancreatic juices containing enzymes which are secreted into the small intestine.

• Hormones which are secreted from the islet of Langerhans into the blood.

Exocrine glands secrete substances into a duct. Most cells in the pancreas synthesize and release digestive enzymes. This is the endocrine function of the pancreas.

The endocrine cells are in small groups surrounding tiny tubules. Each group of cells are called an acinus. The acini are grouped into small lobules separated by connective tissue. The cells of the acini secrete the enzymes they synthesize into the tubule at the center of the group.

The tubules from the acini join to form intralobular ducts that eventually combine to make up the pancreatic duct. The pancreatic duct carries the fluid containing the enzymes into the first part of the small intestine.

The fluid from the pancreatic duct contains the following enzymes:

• Pancreatic amylase -  a carbohydrase which digests amylose to maltose.
• Trypsinogen -  An inactive protease which will be converted to the active form trypsin when it enters the small intestine.
• Lipase- Digests lipid molecules.

The fluid also contains sodium hydrogencarbonate, which makes it alkaline. This helps to neutralize the contents of the digestive system that have just left the acid environment of the stomach.

• Dispersed in small patches among the lobules of acini are the islets of Langerhans.

• The islets of Langerhans contain the alpha cells and the beta cells that make up the endocrine tissue in the pancreas.

• The alpha cells secrete glucagon and the beta cells secrete insulin.

• When insulin is secreted from the beta cells in the islets of Langerhans, it brings about effects that reduce blood glucose concentration.

• If the blood glucose concentration is too high then it is important that insulin is released from the beta cells.

• However, if the blood glucose concentration drops too low it is important that insulin secretion stops.

• The cell membrane of the beta cells contain both calcium ion channels and potassium ion channels.

• The potassium ion channels are normally open and the calcium ion channels are normally closed. Potassium ions diffuse out of the cell making the inside of the cell, more negative, at rest the potential difference across the membrane is about  -70mV.

• When glucose concentrations outside the cell are high, glucose molecules move into the cell.

• The glucose is quickly used in metabolism to produce ATP. This involves the enzyme glucokinase.

• The extra ATP causes the potassium channels to close.

• The potassium can no longer diffuse out, and this alters the potential difference across the cell membrane-it becomes less negative inside.

• This change in potential difference opens the calcium ion channels.

• Calcium ions enter the cell and cause the secretion of insulin by making the vesicles containing insulin move to the cell surface membrane and fuse with it, releasing insulin by exocytosis.

The concentration of blood glucose is carefully regulated. The normal blood concentration of glucose is between 4 and 6 mmol dm-3

The cells in the islet of Langerhans constantly monitor the concentrations of glucose in the blood. If the concentration is too high or low then the alpha and beta cells in the islet of Langerhans detect the change and respond by releasing the relevant hormone: insulin if its too high, glucagon is it's too low.

 These hormones act on the cells in the liver (hepatocytes) which can store glucose in the form of glycogen. When there is excess glucose in the blood it is converted to glycogen. If glucose is needed to raise the blood concentration then glycogen is converted back to glucose.

If a person's blood glucose concentration drops bellow 4mmol dm-3 and remains low for long periods the person is said to be hypoglycaemic. The main problem with hypoglycemia is an inadequate delivery of glucose to the body and tissues, in particular, to the brain. Mild hypoglycemia may cause tiredness and irritability. However, in severe cases, there may lead to impairment of brain function and confusion, which may lead to seizures, unconsciousness and even death.

If blood glucose concentration is too high for long periods the person is said to be hyperglycaemic. Permanently high blood glucose concentration can lead to significant organ damage. A blood glucose concentration that consistently above 7mmol dm-3 is used as the diagnosis for diabetes mellitus.

A high blood glucose concentration is detected by the beta cells in the islet of Langerhans. They respond by secreting insulin into the circulatory system so it gets to its target cells in the liver and muscles.

Insulin is a non-steroid hormone so it cannot pass through the cell surface membrane. The target cells possess the specific membrane-bound receptors for insulin. When insulin binds to the insulin receptor, this activates the enzyme tyrosine kinase which is associated with the receptor on the inside of the membrane.

Tyrosine kinase causes phosphorylation of inactive enzymes leading to a cascade of enzyme controlled reactions inside the cell.

• More transporter proteins specific to glucose are placed into the cell surface membrane. This is achieved by causing vesicles containing these transporter proteins to fuse with the membrane.

• More glucose enters the cell.

• Glucose in the cell is converted to glycogen for storage (glycogenesis)

• More glucose is converted to fats.

• More glucose is used in respiration.

The increased uptake of glucose, through the specific transporter proteins, reduces the blood glucose concentration.

A low blood glucose concentration is detected by the alpha cells in the islets of Langerhans. They secrete glucagon into the blood.

Glucagon is a non-steroid hormone and its target cells are the hepatocytes, which have the specific receptor for glucagon.

When the blood passes these cells the glucagon binds to a receptor, stimulating a G protein that activates the adenyl cyclase.

The adenyl cyclase converts ATP to cAMP, which activates a series of enzyme controlled reactions:

• Glycogen is converted to glucose (glycogenolysis) by phosphorylase A, which is one of the enzymes activated in the cascade.
• More fatty acids are used in respiration.
• Amino acids and fats are converted into additional glucose, by gluconeogenesis.

The overall effect is that blood glucose concentration increases.

Diabetes mellitus is a condition in which the body is no longer able to produce sufficient insulin to control its blood glucose concentrations.

This can lead to prolonged very high concentrations of glucose ( hyperglycaemia) after a meal rich in sugars and other carbohydrates.

It can also lead to the concentration dropping too low (hypoglycaemia) after exercise or after fasting.

It usually starts in childhood. It is thought to be the result of an autoimmune response in which the body's immune system attacks and destroys the beta cells. It may also result from a viral attack.

In a healthy person, glucose is absorbed into the blood and any excess is converted to glycogen in the liver and muscles. This glycogen can then be used to release glucose when blood glucose concentration falls.

A person with type 1 diabetes is no longer able to synthesize sufficient insulin and cannot store excess glucose as glycogen. Excess glucose in the blood is not removed quickly, leaving a prolonged period of high glucose concentration. However, when the blood glucose falls, there is no store of glycogen that can be used to release glucose. Therefore the blood glucose concentration is too low. This is when a diabetic person can suffer a "hypo" - a period of hypoglycemia.

A person with type 2 diabetes can produce insulin, but not enough. Also as people age, their responsiveness to insulin declines.

This is probably because the specific receptors on the surface of their liver and muscle cells are less responsive and their cells lose their ability to respond to insulin in the blood.

In type 2 diabetes the blood glucose concentration is almost permanently raised, which can damage major organs and circulation.

Certain factors seem to bring on early-onset type 2 diabetes, these include:

• Obesity
• Lack of regular exercise.
• A high sugar diet, particularly refined sugars.
• Being of Asian or Afro-Caribbean origin.
• Family history.

Type 1 diabetes is usually treated using insulin injections. The blood glucose concentrations must be monitored and the correct dose of insulin administered to keep the glucose concentration relatively stable. 

Alternatives to insulin injections include:

• Insulin pump therapy - A small device constantly pumps insulin into the bloodstream from a needle that is inserted under the skin permanently.

• Islet cell transplantation- Healthy beta cells from the pancreas of a deceased donor are implanted into the pancreas of someone with type 1 diabetes.

• A complete pancreas transplant.

Recent research has shown that it may be possible to treat type 1 diabetes using stem cells to grow new islets of Langerhans in the pancreas. Stem cells are not yet differentiated and can be induced to develop into a variety of cell types.

The most common sources of stem cells are bone marrow and the placenta. However, scientists have found precursor cells in the pancreas of adult mice. These cells are capable of developing into a variety of cell types and may be true stem cells. If similar cells can be found in the human pancreas then they could be used to produce new beta cells in patients with type 1 diabetes. This would give the patient freedom from daily insulin injections.

Type 2 diabetes is usually treated by changes in lifestyle. 

A type 2 diabetic will be advised to lose weight, exercise regularly and carefully monitor their diet, taking care to match carbohydrate intake and use.

This may be supplemented by medication that reduces the amount of glucose the liver releases into the bloodstream or that boosts the amount of insulin released by the pancreas.

In severe cases, further treatment may include insulin injections or the use of other drugs that slow down the absorption of glucose from the digestive system.

Insulin used to be extracted from the pancreas of animals -  usually from pigs as this matches human insulin most closely. However, more recently,  human insulin has been produced by genetically modified e.coli.

The advantages of using insulin from genetically modified bacteria include:

• It's an exact copy of human insulin, so it is faster acting and more effective.
• Less chance of developing tolerance to insulin.
• There is less chance of rejection due to an immune response.
• There is a lower risk of infection.
• It's cheaper to manufacture the insulin then extract it from animals.
• The manufacturing process is more adaptable to demand.
• Some people are less likely to have moral objections to using the insulin produced from bacteria than to using that extracted from animals.