Hormonal Communication

Protein and peptide hormones, and derivatives of amino acids

e.g. adrenaline, insulin and glucagon

Not soluble in the phospholipid membrane and do not enter the cell. They need to bind to the cell surface membrane and release a 2nd messenger inside the cell.

Steriod hormones

e.g. oestrogen and testosterone

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. 

Examples in the human body include:

Pituitary Gland

Thyroid Gland

Thymus

Adrenal Glands

Pancreas

Ovaries/Testes

Hormones always have a specific function- they are transported all over the body, they have an effect on one type of tissue. The cells receiving an endocrine signal are called target cells. These cells may be grouped together in a target tissue such as the epithelium of the collecting ducts. Alternatively they may be more widely dispersed in a number of tissues, such as the receptors for adrenalin found in the CNS including the heart and the tissues innervated by the peripheral nervous system including the heart, smooth muscle and skeletal muscle.

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. 

Non-steroid hormones are known as first messengers. They are signalling molecules outside the cell that bind to the cell surface membrane and initiate an effect inside the cell. They usually cause the release of another signalling molecule in the cell, which is 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 to 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 cyclic AMP (cAMP). This second messenger may act directly on another protein (such as an ion channel), or it may initiate a cascade of enzyme-controlled reactions that alter the activity of the cell.

They are found lying anterior to (just above) the kidneys.

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 the blood vessels.

The adrenal glan 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

Found in the centre 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 action of steroid hormones can be summarised as followed:

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

2. The steroid hormone binds with a specific receptor in the cytoplasm.

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

4. Binding stimulated the production of messenger RNA molecules, which code for the production of proteins.

Mineralocorticoids help to control the concentration of Na and K in the blood.

As a results 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 Na+, decreases absorption of K+ ions and increases water retention so increases 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 a 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 development of the secondary sexual characteristics and regulate the production of gametes.

Adrenaline is a polar molecule derived from the amino acid tyrosine.

This means that it cannot enter cells through the plasma membrane like a steroid hormone can.

Therefore, it must be detected by specialised receptors on the plasma membrane of the target cells. Many cells and tissues have adrenaline receptors. Therefore the effects of adrenaline are widespread. The role of adrenaline is to prepare the body for activity, which includes the following effects:

• relaxing smooth muscle in the bronchioles
• increases SV and HR
• 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

A small organ lying just below the stomach.

It is unusual in that it has both exocrine and endocrine functions.

The 2 main secretions of the pancreas are:

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

•hormones which are secreted from the islets of Langerhans into the blood.

Exocrine glands secrete substances into a duct. Most cells in the pancreas synthesise and release digestive enzymes. This is the exocrine function of the pancreas. The exocrine cells are in small groups surrounding tiny tubules. Each group of cells is called an acinus. The acini are grouped together into small lobules separated by connective tissue. The cells of the acini secrete the enzymes they synthesise into the tubule at the centre 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 (duodenum). 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 duodenum.

•Lipase- which digests lipid molecules.

•Sodium hydorgencarbonate- makes it alkaline, neutralises 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 and the islets of Langerhans.

The islets of Langerhans contain alpha cells which secrete glucagon and beta cells which secrete insulin.  

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

1. The cell membranes of the beta cells contain both Ca2+ ion channels and K+ ion channels.

2. The K+ ion channels are normally open and the Ca2+ ion channels are normally closed. K+ ions diffuse out of the cell making the inside of the cell more -ve, potential difference across the cell membrane is -70mV.

3. When glucose concentration outside the cell are high, glucose molecules move into the cell.

4. The glucose is quickly used in metabolism to produce ATP. It involves glucokinase.

5. The extra ATP causes the K+ channels to close.

6. The K can no longer diffuse out and this alters the potential difference across the cell membrane- it becomes less negative inside (-30mV).

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

8. 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 normal blood concentration of glucose is between 4 and 6 mmol dm-3. If a person's blood glucose drops below 4mmol dm-3 and remains too low for long periods, the person is said to be hypoglycaemic. Mainly caused by hypoglycaemia- an inadequate delivery of glucose to the body tissues and to the brain. Mildly- tiredness and irritability. Severely- impairment to brain function, confusion, seizures, unconsciousness and even death. 

If blood glucose concentration is allowed to rise too high for long periods, it is a condition called hyperglycaemia. If this is permanent, it can lead to significant organ damage. Blood glucose concentrations of more than 7 are used as the diagnosis for diabetes mellitus.

The cells in the islets of Langerhans constantly monitor the blood glucose concentration. If it falls away or rises from the acceptable concentration then the alpha and beta cells in the islets of Langerhans detect the change and respond by releasing the relevant hormone- insulin if BG is high and glucagon if it is 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.

A high blood glucose concentration is detected by the beta cells. They respond by secreting insulin into the blood. Insulin travels throughout the body in the circulatory system. The target cells are the liver cells, muscle cells and some other body cells including those in the brain.

Human insulin is a small protein of 51 amino acids, therefore it is unable to 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 in the cell. This activates the enzymes leading to a cascade of enzyme-controlled reactions inside the cell.

Insulin has several effects on 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.
• Glycogenesis.
• More glucose is converted into fats and more is used in respiration.

A low blood glucose concentration is detected by the alpha cells in the islets of Langerhans. The alpha cells then secrete glucagon into the blood. Glucagon is a small protein containing 29 amino acids. Its target cells are the hepatocytes, which possess the specific receptor for glucagon. When the blood passes these cells the glucagon binds to the receptors. This stimulates a G protein inside the membrane, which activates the adenyl cyclase inside each cell. The adenyl cyclase converts ATP to cAMP, which activates a series of enzyme-controlled reactions in the cell.

The effects of glucagon include the following: 

• Glycogen is converted to glucose 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 concentration of glood glucose is controlled by a negative feedback mechanism involving the hormones insulin and glucagon.

These hormones are antagonistic.

One of their effects is to inhibit the effects of the opposing hormone.

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

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 exercising or fasting.

Also known as insulin dependent diabetes or juvenile-onset diabetes because it usually starts in childhood. It is thought to be an autoimmune response in which the body attacks itself and destroys the beta cells. It may also be a 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 concentrations fall. 

A person with type 1 diabetes is no longer able to synthesise sufficient insulin and cannot store excess glucose as glycogen. Excess glucose in the blood is not removed quickly, leaving a prolonged period of high 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 falls too low, this is when the person can suffer from a period of hypoglaemia.

Also known as non-insulin dependent diabetes. A person with type 2 diabetes can produce insulin but not enough. Also, as people age their responsiveness to insulin declines, this is because the specific receptors on the surface of the liver and muscle cells become less responsive and the cells lose their ability to respond to the insulin in the blood.

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

Other causes include:

•obesity

•lack of regular exercise

•high diet in sugars (especially refined sugars)

•being Asian or Afro-Caribbean in origin

•family history

• Usually treated by insulin injections (long acting - 24 hours, short acting -8 hours, or rapid acting).
• Insulin pump therapy- a small device constantly pumps insulin (at a controlled rate) into the bloodstream through a needle that is permanently inserted under the skin.
• Islet cell transplant- healthy beta cells from the pancreas of a deceased donor are implanted into the pancreas of someone with type 1 diabetes.
• A pancreas translant
• Stem cells- to grow into new islets of Langerhans. Stem cells are not yet differentiated and can be induced to develop into a variety of cell types. 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.

Usually treated with changes in lifestyle. A type 2 diabetic will be advised to lose weight, exercise regularly and monitor their diet. This may be supplemented by medication that reduces the amount of glucose the liver releases to the blood stream or that boosts the amount of insulin released to 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, normally pigs as their insulin matches human insulin most closely. However, more recently, insulin has been produced by Escherichia coli bacteria that have undergone genetic modification to manufacture human insulin. Here are the advantages:

•Exact copy of human insulin, faster acting and more effective.

•Less chance of developing an intolerance to insulin.

•Less chance of rejection due to an immune response.

•Lower risk of infection.

•It is cheaper to manufacture the insulin than to 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.