Hormonal Control

AQA spec ref: 3.6.3 - Hormonal communication

Hormones are chemical messengers released by endocrine glands directly into the blood and carried to target organs. Hormonal control is slower than nervous control (takes seconds to minutes rather than milliseconds), but affects a wider range of tissues for longer periods. The two systems work together - the hypothalamus links them, and the adrenal gland produces both hormones (adrenaline) and acts on nervous-system cues.

Comparison: Nervous vs Hormonal Communication

The Endocrine System - Key Glands

Hypothalamus: releases releasing hormones and inhibiting hormones that regulate the pituitary gland. It links the nervous system to the endocrine system. The hypothalamus detects changes in blood composition (temperature, glucose, osmotic pressure) and responds by releasing hormones.

Pituitary gland (master gland):

• Anterior pituitary - releases tropic hormones (TSH, ACTH, FSH, LH, growth hormone) that control other glands
• Posterior pituitary - stores and releases ADH (antidiuretic hormone) and oxytocin (actually produced by hypothalamus)

Adrenal glands (above kidneys):

• Adrenal cortex (outer) - produces steroid hormones: cortisol (stress/anti-inflammatory), aldosterone (salt/water balance)
• Adrenal medulla (inner) - produces adrenaline and noradrenaline (catecholamines, rapid stress response)

Pancreas (both endocrine and exocrine):

• Islets of Langerhans contain alpha cells (glucagon) and beta cells (insulin)

Thyroid: produces thyroxine - regulates metabolic rate, growth, and development.

Gonads: testes (testosterone), ovaries (oestrogen, progesterone) - reproductive and secondary sex characteristic development.

How Hormones Work: First and Second Messengers

Hormones cannot all enter cells directly. Their mechanism depends on whether they are water-soluble or lipid-soluble:

Lipid-soluble hormones (e.g. steroid hormones, thyroxine):

• Can diffuse directly through the phospholipid bilayer
• Bind to intracellular receptors (in cytoplasm or nucleus)
• The hormone-receptor complex acts as a transcription factor - it binds to DNA and activates or represses specific genes
• Effect: changes in gene expression→changed protein synthesis→slow but long-lasting response

Water-soluble hormones (e.g. adrenaline, insulin, glucagon, ADH):

• Cannot cross the phospholipid bilayer
• Bind to cell surface receptors (glycoproteins on plasma membrane)
• Use a second messenger system to relay the signal inside the cell

Second messenger mechanism (e.g. adrenaline via cAMP):

1. Adrenaline (first messenger) binds to a G protein-coupled receptor on the cell surface
2. This activates a G protein, which activates adenylyl cyclase (adenylate cyclase)
3. Adenylyl cyclase converts ATP→cyclic AMP (cAMP) - the second messenger
4. cAMP activates protein kinase A, which phosphorylates (activates) target enzymes
5. This triggers a cascade of enzyme activations - amplifying the original signal enormously (one hormone molecule can produce millions of product molecules)
6. The response is rapid (because no gene expression is involved - existing proteins are just activated)
7. cAMP is rapidly broken down by phosphodiesterase to terminate the signal

Adrenaline and the Fight-or-Flight Response

Adrenaline is released by the adrenal medulla in response to stress, fear, or exercise. It prepares the body for rapid physical action:

Effects of adrenaline:

• Increases heart rate and cardiac output→more blood to muscles
• Causes glycogenolysis in liver (glycogen→glucose)→raises blood glucose for energy
• Dilates bronchioles→more air to lungs
• Dilates blood vessels to skeletal muscles; constricts blood vessels to gut and skin → blood redirected to muscles
• Dilates pupils
• Stimulates gluconeogenesis (glucose from non-carbohydrate sources)

Mechanism in liver cells: adrenaline → binds receptor → G protein → adenylyl cyclase → cAMP → protein kinase A → activates phosphorylase kinase → activates glycogen phosphorylase → breaks down glycogen → glucose released.

This is an example of signal amplification: one adrenaline molecule triggers a cascade that can release millions of glucose molecules.

Control of Blood Glucose - Insulin and Glucagon

Maintaining blood glucose at ~4 - 6 mmol/L is critical: glucose is the primary fuel for brain cells (which cannot use fatty acids), and hyperglycaemia damages blood vessels and nerves.

This is a classic negative feedback system:

When Blood Glucose Rises (e.g. after a meal)

1. Glucose detected by beta cells of the islets of Langerhans in the pancreas
2. Insulin is secreted into the blood
3. Insulin binds to cell surface receptors on liver, muscle, and adipose cells
4. Effects:

• Increases uptake of glucose by cells (more GLUT4 glucose transporters inserted into cell membranes - especially in muscle and adipose tissue)
• Stimulates glycogenesis (glucose→glycogen) in liver and muscle
• Stimulates glucose oxidation in respiration
• Inhibits gluconeogenesis and glycogenolysis

1. Blood glucose falls back to normal→insulin secretion stops (negative feedback)

When Blood Glucose Falls (e.g. during fasting)

1. Glucose levels fall→detected by alpha cells of the islets of Langerhans
2. Glucagon is secreted into the blood
3. Glucagon binds to liver cell receptors (via G protein→cAMP→protein kinase A cascade)
4. Effects:

• Stimulates glycogenolysis (glycogen→glucose) in liver
• Stimulates gluconeogenesis (amino acids+glycerol→glucose)

1. Blood glucose rises back to normal→glucagon secretion stops (negative feedback)

Diabetes Mellitus

Type 1 diabetes: an autoimmune condition in which the immune system destroys the beta cells of the pancreatic islets. No insulin is produced. Blood glucose rises uncontrollably after meals. Treatment: insulin injections or insulin pump.

Type 2 diabetes: insulin is produced but target cells become insensitive to it (insulin resistance) - receptors on target cells no longer respond normally to insulin. Initially treated with lifestyle changes (diet, exercise), then oral medication (e.g. metformin), and sometimes insulin injections in advanced cases. Strongly linked to obesity, lack of exercise, and genetic factors. The TCF7L2 gene is the strongest known genetic risk factor - highly relevant to your EPQ on South Asian metabolic disease risk.

Kidney Structure

Kidney Structure

Each kidney consists of an outer cortex and inner medulla, surrounded by a tough fibrous capsule, with the renal pelvis funnelling urine into the ureter. The functional unit is the nephron (~1 million per kidney), which spans both regions - this cortex - medulla arrangement is what establishes the salt gradient required for water reabsorption via the counter-current multiplier.

Features and Functions

• Cortex - outer region; contains Bowman's capsules, PCTs, and DCTs where ultrafiltration and most selective reabsorption occur.
• Medulla - inner region; houses the loops of Henle and collecting ducts, and maintains the salt gradient for water reabsorption.
• Renal capsule - tough fibrous outer layer; protects the kidney from mechanical damage and infection.
• Renal pelvis - funnel-shaped cavity; collects urine from collecting ducts and channels it into the ureter.
• Nephron - functional unit of the kidney; carries out ultrafiltration, selective reabsorption, and osmoregulation to form urine.
• Bowman's capsule - cup-shaped structure around the glomerulus; site of ultrafiltration of blood under high hydrostatic pressure.
• Glomerulus - knot of capillaries inside Bowman's capsule; provides the high-pressure blood supply that drives filtration.
• Proximal convoluted tubule (PCT) - folded/microvilli-lined tubule in the cortex; site of selective reabsorption of glucose, amino acids, and ~85% of water/ions via co-transport with Na⁺.
• Loop of Henle - hairpin loop into the medulla; sets up a salt (Na⁺/Cl⁻) gradient in the medulla via the counter-current multiplier, enabling water reabsorption from the collecting duct.
• Distal convoluted tubule (DCT) - tubule in the cortex; site of fine-tuned ion balance (Na⁺/K⁺) under aldosterone control.
• Collecting duct - passes through the medulla to the renal pelvis; water reabsorption here is controlled by ADH, which inserts aquaporins to adjust urine concentration.
• Ureter - muscular tube; carries urine from the renal pelvis to the bladder.

ADH and Osmoregulation

Antidiuretic hormone (ADH) controls water reabsorption in the kidney to maintain blood osmotic pressure. It is produced by the hypothalamus and released from the posterior pituitary gland.

When blood water potential falls (blood becomes too concentrated - e.g. dehydration, sweating):

1. Osmoreceptors in the hypothalamus detect the change
2. ADH is released from the posterior pituitary into the blood
3. ADH travels to the kidneys, binds to receptors on the collecting duct and distal convoluted tubule
4. The binding triggers insertion of aquaporins (water channel proteins) into the apical membrane - via a second messenger cascade (cAMP)
5. More water is reabsorbed by osmosis from the tubule into the blood
6. Concentrated (small volume) urine is produced
7. Blood osmotic pressure returns to normal→ADH secretion falls (negative feedback)

When blood water potential rises (blood too dilute - e.g. drinking a lot of water):

1. ADH secretion decreases
2. Fewer aquaporins in collecting duct membrane
3. Less water reabsorbed
4. Dilute (large volume) urine produced

Alcohol inhibits ADH release → less water reabsorption → large volumes of dilute urine → dehydration.

Summary

• Hormones: released by endocrine glands, travel in blood, act on target cells with specific receptors
• Lipid-soluble hormones→diffuse through membrane→intracellular receptor→alter gene expression (slow, long-lasting)
• Water-soluble hormones → cell surface receptor → second messenger (cAMP) → enzyme cascade → rapid response; signal amplification
• Adrenaline: fight-or-flight; glycogenolysis; second messenger = cAMP; protein kinase A cascade
• Blood glucose: raised glucose → insulin (beta cells) → glycogenesis + increased uptake; lowered glucose → glucagon (alpha cells) → glycogenolysis + gluconeogenesis
• Diabetes: Type 1 = no insulin (beta cell destruction); Type 2 = insulin resistance
• ADH: low blood water potential→ADH released→aquaporins inserted into collecting duct→more water reabsorbed

AQA Exam Tips

• Second messenger: cAMP is the classic second messenger for adrenaline and glucagon. Always state: hormone binds surface receptor → adenylyl cyclase activated → ATP → cAMP → protein kinase A → target enzyme activated.
• Amplification: one hormone molecule activates one adenylyl cyclase → many cAMP → many kinase activations → millions of product molecules. AQA loves asking why a tiny concentration of hormone produces a large effect.
• Insulin mechanism of action: insulin increases the number of GLUT4 glucose transporters in the cell membrane → faster facilitated diffusion of glucose into the cell.
• Negative feedback loop: state clearly: rise in X → response to lower X → X returns to normal → response stops. Apply to blood glucose control with specific hormones.
• Type 1 vs Type 2 difference: Type 1 = no insulin produced (autoimmune, insulin injections needed); Type 2 = insulin produced but insufficient/ignored (insulin resistance, lifestyle-related). AQA asks you to distinguish them.
• ADH and aquaporins: ADH does not open existing aquaporins - it causes NEW aquaporins to be inserted into the cell membrane. This is the mechanism that increases permeability.
• Osmoregulation location: ADH acts on the collecting duct and distal convoluted tubule of the nephron in the kidney.