describe the features of the endocrine system with reference to the hormones ADH, glucagon and insulin (see 14.1.8, 14.1.9 and 14.1.10)

Control and Coordination in Mammals

Objective

Describe the features of the endocrine system with reference to the hormones antidiuretic hormone (ADH), glucagon and insulin (Cambridge AS & A Level Biology syllabus points 14.1.8, 14.1.9 and 14.1.10).

1. Syllabus Requirements (Topic 14 – Control and Coordination)

• 14.1.1 – Major endocrine glands and their principal hormones

  • Hypothalamus (releasing/inhibiting hormones, ADH, oxytocin)
  • Anterior pituitary (GH, ACTH, TSH, LH, FSH, prolactin)
  • Posterior pituitary (ADH, oxytocin)
  • Thyroid (thyroxine T₄, triiodothyronine T₃, calcitonin)
  • Parathyroid (parathyroid hormone – PTH)
  • Adrenal cortex (cortisol, aldosterone, androgens)
  • Adrenal medulla (adrenaline, noradrenaline)
  • Pancreas (insulin, glucagon, somatostatin)
  • Gonads (estrogen, progesterone, testosterone)
  • Specialised renal cells (renin, erythropoietin)

• 14.1.2 – Classification of hormones

  • Peptide / protein hormones (e.g., ADH, insulin, glucagon)
  • Steroid hormones (e.g., cortisol, estrogen)
  • Amine hormones (e.g., adrenaline, thyroxine)

• 14.1.3 – Mechanisms of action

  • Cell‑surface receptors (GPCR, receptor tyrosine kinase)
  • Second‑messenger systems (cAMP, IP₃/DAG, Ca²⁺)
  • Intracellular/nuclear receptors (steroid hormones)
  • Phosphorylation cascades and changes in gene expression

• 14.1.4 – Homeostatic control

  • Set‑point, sensors, integrators, effectors, negative‑feedback loops

• 14.1.5 – Neuro‑endocrine integration

  • Hypothalamic‑pituitary axes
  • Autonomic influences (e.g., adrenal medulla)

• 14.1.8, 14.1.9, 14.1.10 – Detailed study of ADH, glucagon and insulin

2. How the Notes Meet the Syllabus Requirements

3. Overview of the Endocrine System

3.1 General Features

• Endocrine glands secrete hormones directly into the bloodstream; hormones travel to distant target cells that possess specific receptors.
• Hormone classification

  • Peptide / protein – water‑soluble, act via cell‑surface receptors (e.g., ADH, insulin, glucagon).
  • Steroid – lipid‑soluble, cross the membrane and bind intracellular receptors that act as transcription factors.
  • Amine – derived from amino acids; some act via surface receptors (adrenaline) and others via nuclear receptors (thyroxine).

• Signal transduction

  • Ligand binds receptor → activation of a second‑messenger system (cAMP, IP₃/DAG, Ca²⁺) or direct tyrosine‑kinase cascade.
  • Resulting cascade modifies enzyme activity, ion‑channel permeability or gene expression, producing the physiological response.

• Homeostasis – Hormones act as effectors in negative‑feedback loops:

  1. Sensor (e.g., osmoreceptor, pancreatic β‑cell)
  2. Integrator (hypothalamus or pancreas)
  3. Effector hormone
  4. Response that returns the variable toward its set‑point.

• Neuro‑endocrine integration

  • Hypothalamus releases releasing or inhibiting hormones to the anterior pituitary.
  • Posterior pituitary stores hormones (ADH, oxytocin) synthesised in hypothalamic neuro‑secretory cells.
  • Adrenal medulla functions as a modified sympathetic ganglion, releasing adrenaline under direct neural control.

4. Detailed Study of ADH, Glucagon and Insulin

4.1 Antidiuretic Hormone (ADH, Vasopressin)

• Source & classification – Synthesised in the supra‑optic and paraventricular nuclei of the hypothalamus; stored and released from the posterior pituitary. Peptide hormone (9‑amino‑acid).
• Receptor type – V₁ (vascular smooth muscle) and V₂ (renal collecting duct) G‑protein‑coupled receptors (GPCR).
• Renal V₂ signalling (cAMP pathway)

  1. ADH binds V₂ → Gₛ activation.
  2. ↑ Adenylate cyclase → ↑ cAMP.
  3. cAMP activates protein kinase A (PKA).
  4. PKA phosphorylates aquaporin‑2 (AQP2)‑containing vesicles.
  5. Vesicles fuse with the apical membrane → insertion of AQP2 channels → ↑ water re‑absorption.

• Target organs – Kidney collecting ducts (principal cells); vascular smooth muscle (vasoconstriction).
• Principal effect – Increases water permeability → concentrated urine, reduced urine volume, raised blood volume and arterial pressure.
• Regulation

  • Primary: plasma osmolality (osmoreceptors in the hypothalamus). A 1 % rise in osmolality ≈ 1 mOsm kg⁻¹ triggers a measurable ADH surge.
  • Secondary: arterial pressure/volume via baroreceptors (low pressure → ↑ ADH release).

• Quantitative example – Normal plasma ADH ≈ 1–5 pg mL⁻¹; severe dehydration can raise it to > 20 pg mL⁻¹.
• Clinical relevance

  • Deficiency → central diabetes insipidus (polyuria, polydipsia, dilute urine, ↑ plasma osmolality).
  • Excess → syndrome of inappropriate ADH (SIADH) → hyponatraemia, water intoxication.

4.2 Glucagon

• Source & classification – α‑cells of the pancreatic islets of Langerhans; peptide hormone (29 aa).
• Receptor type – Glucagon receptor: Gₛ‑coupled GPCR.
• Hepatic signalling (cAMP/PKA)

  1. Glucagon binds receptor → Gₛ activation.
  2. ↑ Adenylate cyclase → ↑ cAMP.
  3. cAMP activates PKA.
  4. PKA phosphorylates:

     • Phosphorylase kinase → activates glycogen phosphorylase → glycogenolysis.
     • Fructose‑1,6‑bisphosphatase → stimulates gluconeogenesis.

  5. PKA also inhibits glycolytic enzymes (PFK‑1) and activates glucose‑6‑phosphatase, producing net glucose output.

• Target organs – Liver (major), kidney (proximal tubule), adipose tissue (lipolysis).
• Principal effect – Raises blood glucose by stimulating glycogen breakdown and new glucose synthesis.
• Regulation

  • Stimulus: low plasma glucose (< 4 mmol L⁻¹) sensed by α‑cells.
  • Inhibition: high glucose, insulin, somatostatin, sympathetic α₂‑adrenergic input.

• Quantitative example – Fasting plasma glucagon ≈ 50–150 pg mL⁻¹; after a 12‑h fast it can exceed 250 pg mL⁻¹.
• Clinical relevance

  • Therapeutic injection for severe hypoglycaemia.
  • Chronic hyperglucagonaemia contributes to hyperglycaemia in type 2 diabetes.

4.3 Insulin

• Source & classification – β‑cells of pancreatic islets; peptide hormone (51 aa) derived from pro‑insulin.
• Receptor type – Insulin receptor: a receptor tyrosine kinase (RTK) that autophosphorylates on tyrosine residues.
• Signal transduction (PI3K‑Akt pathway) in muscle & adipose

  1. Insulin binds α‑subunits → β‑subunit tyrosine‑kinase activity.
  2. Autophosphorylation creates docking sites for IRS (insulin‑receptor substrate) proteins.
  3. IRS activates phosphoinositide‑3‑kinase (PI3K) → conversion of PIP₂ to PIP₃.
  4. PIP₃ recruits and activates Akt (PKB).
  5. Akt phosphorylates:

     • AS160 → translocation of GLUT4‑containing vesicles to the plasma membrane (↑ glucose uptake).
     • Glycogen synthase kinase‑3 (inhibition) → activation of glycogen synthase (glycogenesis).

• Target organs – Liver, skeletal muscle, cardiac muscle, adipose tissue.
• Principal effects

  • Facilitates cellular glucose uptake (GLUT4).
  • Stimulates glycogen synthesis.
  • Promotes lipogenesis & inhibits lipolysis.
  • Enhances protein synthesis and suppresses proteolysis.

• Regulation

  • Stimulus: rise in plasma glucose > 5 mmol L⁻¹ (especially after a carbohydrate‑rich meal).
  • Modulators: incretin hormones (GLP‑1, GIP) augment secretion; glucagon, sympathetic α₂‑adrenergic activity and somatostatin suppress it.

• Quantitative example – Post‑prandial insulin peaks ≈ 50–150 µU mL⁻¹ (≈ 300–900 pmol L⁻¹) within 30 min.
• Clinical relevance

  • Type 1 diabetes – autoimmune destruction of β‑cells → absolute insulin deficiency.
  • Type 2 diabetes – peripheral insulin resistance + relative β‑cell failure.
  • Insulin therapy (rapid‑acting, long‑acting analogues) and monitoring via blood glucose or HbA₁c.

5. Practical / Investigation Box (AO3)

6. Comparison of ADH, Glucagon and Insulin

7. Integrated Feedback Example: Blood‑Glucose Homeostasis

The interplay of insulin and glucagon maintains plasma glucose within a narrow set‑point (≈ 4–6 mmol L⁻¹). The loop can be summarised:

When [Glucose] ↑  →  β‑cells release insulin ↑  →  ↑ GLUT4 translocation & glycogen synthesis  →  [Glucose] ↓
When [Glucose] ↓  →  α‑cells release glucagon ↑  →  ↑ glycogenolysis & gluconeogenesis  →  [Glucose] ↑

Both hormones are subject to negative‑feedback: the deviation from the set‑point triggers secretion that opposes the change, restoring equilibrium.

Suggested Diagram

Draw a flow‑chart showing (1) blood‑glucose sensor (pancreatic α‑ and β‑cells), (2) hormonal responses (insulin vs. glucagon), (3) target‑organ actions (muscle, liver, adipose), and (4) feedback inhibition when glucose returns to normal.

8. Key Points to Remember

1. The endocrine system uses chemical messengers that act more slowly but for a longer duration than nerve impulses.
2. ADH, glucagon and insulin illustrate three major hormone classes (peptide‑GPCR, peptide‑GPCR, peptide‑RTK) and three distinct physiological roles: water balance, glucose mobilisation, and glucose utilisation.
3. All three hormones operate within negative‑feedback loops that keep internal variables (osmolality, blood glucose, blood volume) close to their set‑points.
4. Understanding the source, receptor type, signalling cascade and regulation of each hormone is essential for answering both factual (AO1) and applied (AO2/3) exam questions.