5.4- hormonal communication

What is the endocrine system

What is the endocrine system

A communication system using hormones as signalling molecules

What are hormones?

Molecules (proteins or steroids) that are released by endocrine glands directly into the blood

What are target cells?

For non-steroid hormones, cells that possess a specific receptor on their plasma membrane. The shape of the receptor is complementary to the shape of the hormone molecule. Many similar cells together form a target tissue.

What are the two types of hormone?

Protein and peptide hormones, and derivatives of amino acids, e.g. adrenaline, insulin and glucagon

Steroid hormones, e.g. oestrogen and testosterone

Why don’t proteins enter the cell?

They 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 second messenger inside the cell.

Can steroid hormones enter the cell?

Yes- they pass through the membrane and enter the cell and nucleus to have a direct effect on the DNA in the nucleus.

What are endocrine glands?

Ductless glands- they consist of groups of cells that manufacture and release the hormone directly into the blood in capillaries running through the gland.

Detecting the signal

• the cells receiving the endocrine signal are target cells- these can be grouped together in a target tissue such as the epithelium of the collecting ducts, or they can be more widely dispersed in a number of tissues, such as the receptors for adrenaline in the central nervous system

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

• Only specific target cells possessing the correct receptor will respond to the hormone

What are first messengers?

Non-steroid hormones. 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, which is the second messenger- the second messenger stimulates a change of activity in the cell.

The activation of the second messenger

• many non-steroid hormones act via a G protein in the membrane

• The G protein is activated when the hormone binds to the receptor, and in turn it activates an effector molecule- usually an enzyme that converts an inactive molecule into the active second messenger

• In many cells the effector is the enzyme adenyl cyclase, which converts ATP to cyclic AMP

• Cyclic AMP is the second messenger, and it may act directly on another protein or initiate a cascade of enzyme-controlled reactions that alter the activity of the cell

What is each adrenal gland divided into?

• outer adrenal cortex and inner adrenal medulla

What are the three layers of cells in the adrenal cortex?

• zona glomerulosa

• Zona fasciculata

• Zona reticularis

Zona glomerulosa

Outermost layer which secretes mineralocorticoids such as aldosterone

Zona fasciculata

The middle layer, which secretes glucocorticoids such as cortisol

Where is the adrenal medulla and what does it secrete?

At the centre of the adrenal gland, secretes adrenaline and noradrenaline

Describe the action of steroid hormones (4 stages)

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

2. The steroid hormone binds with a specific receptor with a complementary shape 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 stimulates the production of mRNA, which code for the production of proteins

Mineralocorticoids

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 tubule and collecting ducts in the kidney. It increases absorption of sodium ions, decreases absorption of potassium ions, and increases water retention so increases blood pressure.

Glucocorticoids

Help to control the metabolism of carbohydrates, fats and proteins in the liver.

Cortisol

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

Adrenaline

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

• Polar molecule derived from tyrosine- it cannot enter cells through the plasma membrane, so it must be detected by specialised receptors.

• Role is to prepare the body for activity

Effects of adrenaline

• 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

What are the two main secretions of the pancreas?

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

• Hormones which are secreted form the islets of Langerhans into the blood

What do exocrine glands do?

Secrete substances into a duct. Most cells in the pancreas synthesise and release digestive enzymes.

Where are the exocrine glands in the pancreas and what is the exocrine function of the pancreas?

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 duodenum.

What does the fluid from the pancreatic duct contain?

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- digests lipid molecules

Endocrine function of the pancreas

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

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

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

Releasing 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 it is important that insulin is released from the beta cells

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

Describe the stages of insulin being released from the beta cells

1. The cell membranes of the beta cells contain calcium ion channels and potassium ion channels

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

3. When glucose concentrations outside the cell are too high, glucose moves into the cell

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

5. The extra ATP causes the potassium channels to close

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

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.

What is the normal blood concentration of glucose?

Between 4 and 6 mmol dm-3

What happens when blood glucose concentration drops below 4 mmol dm-3?

Hypoglycaemia

What are the problems caused by hypoglycaemia?

Inadequate delivery of glucose to the body tissues and brain. Mild hypoglycaemia may cause tiredness and irritability, but in severe cases there can be an impairment of brain function and confusion, which can lead to seizures, unconsciousness and death.

What happens if blood glucose concentrations rise too high?

Hyperglycaemia. Permanently high blood glucose concentrations can lead to significant organ damage. A blood glucose concentration that is consistently higher than 7 mmol dm-3 is used as the diagnosis for diabetes mellitus.

How is blood glucose concentration monitored?

islets of Langerhans. If concentration rises or falls away from the acceptable concentration then the alpha and beta cells in the islets of Langerhans detect the change and respond by releasing the relevant hormones.

If blood glucose rises too high

• detected by beta cells in the islets of Langerhans

• beta cells 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

What happens when insulin binds to the insulin receptor?

• activation of 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

Effects of insulin on the cell

• more transporter proteins specific to glucose are placed into the cell surface membrane- this is achieved by causing vesicles containing those 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 converted to fats

• more glucose used in respiration

If blood glucose drops too low

• detected by alpha cells in the islets of Langerhans

• alpha cells then secrete glucagon

• glucagon’s target cells are the hepatocytes, which possess the specific receptor for glucagon

• when blood passes these cells the glucagon binds to the receptors inside the membrane, which activates the enzyme adenyl cyclase, which converts ATP to cAMP and activates a series of enzyme controlled reactions

Effects of glucagon

• glycogen converted to glucose - glycogenolysis by phosphorylase A

• more fatty acids used in respiration

• amino acids and fats converted to additional glucose, by gluconeogenesis

What does antagonistic mean?

The hormones have the opposite effect on blood glucose concentration. One of their effects is to inhibit the effects of the opposing hormone.

Describe the mechanism of negative feedback when blood glucose concentration rises too high

• detected in beta cells by islets of Langerhans

• Beta cells secrete insulin into the blood

• Insulin is detected by receptors on liver and muscle cells

• Liver and muscle cells remove glucose from blood and convert glucose to glycogen

• Glucose concentration falls

Describe the mechanism of negative feedback when blood glucose concentration falls too low

• detected by alpha cells in the islets of Langerhans

• Alpha cells secrete glucagon into the blood

• Glucagon is detected by receptors on liver cells

• Liver cells convert glycogen to glucose and release glucose into the blood

• Glucose concentration rises

What is diabetes mellitus?

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 hyperglycaemia after a meal rich in sugars and other carbohydrates, and hypoglycaemia can happen after exercise or fasting. Known as insulin-dependent,

Type 1 diabetes

• thought to be the result of an autoimmune response in which the body’s immune system attacks and destroys the betas cells. May also result from a viral attack.

• 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 blood glucose falls, there is no store of glycogen that can be used to release glucose, so concentration falls too low

Type 2 diabetes

Non-insulin dependent. A person with Type 2 diabetes can produce insulin, but not enough. As people age, their responsiveness to insulin declines, probably because the specific receptors on liver and muscle cells become less responsive. Blood glucose is almost permanently raised, which can damage the major organs and circulation.

Factors inducing the onset of Type 2 diabetes

• obesity

• Lack of regular exercise

• A diet high in sugars, particularly refined sugars

• Being of Asian or Afro-Caribbean origin

• Family history

Treating Type 1 diabetes

Usually treated using insulin injections. The blood glucose concentration must be monitored and the correct dose of insulin administered to keep the glucose concentration stable.

Alternatives to insulin injections

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 transplantation- healthy beta cells from the pancreas of a deceased donor are implanted into the pancreas of someone with Type 1 diabetes

Potential use of stem cells

Could be used to grow new islets of Langerhans in the pancreas.

Treating Type 2 diabetes

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 to the bloodstream or that boosts the amount of insulin released from 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.

Advantages of using insulin from genetically modified bacteria

• exact copy of human insulin, so is faster acting and more effective

• Less chance of developing tolerance to the insulin

• Less chance of rejection due to an immune response

• Lower risk of infection

• Cheaper to manufacture the insulin than to extract it from animals

• 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