C2.1.6 (HL)—Transmembrane vs. intracellular receptors

Transmembrane receptors mediate hydrophilic peptide hormone signals, while intracellular receptors bind lipid-soluble steroid hormones that cross membranes, linking signal detection to a specific target-cell response.

Syllabus
First assessment 2025
Objective
C2.1.6
Level
HL

Exam analysis

Chance of appearing12%of analysed past papers
Latest appearanceMay 2024
Most common paperPaper3
Typical marks3–6

Common command terms

  • Distinguish
  • Outline
  • Compare
  • Contrast
  • Explain
  • Describe

Recent exam appearances

May 2024Paper3 ["HL"] · TZ125[ 6 ]C2.1.6 (HL)—Transmembrane vs. intracellular receptors
May 2023Paper3 ["HL"] · TZ124[ 6 ]C2.1.6 (HL)—Transmembrane vs. intracellular receptors
November 2020Paper3 ["HL"] · TZ024[ 6 ]C2.1.6 (HL)—Transmembrane vs. intracellular receptors
November 2019Paper3 ["HL"] · TZ022(b)[ 3 ]C2.1.6 (HL)—Transmembrane vs. intracellular receptors
May 2019Paper3 ["HL"] · TZ220(d)[ 3 ]C2.1.6 (HL)—Transmembrane vs. intracellular receptors
Practice this objective

Coverage 2013–2024 · Updated 15 Jul 2026

Ligand chemistry determines receptor location

HL only
Two-panel receptor comparison. Left: hydrophilic ligand binding a transmembrane receptor with polar and non-polar receptor regions labelled. Right: steroid/thyroid hormone crossing the membrane and binding a cytoplasmic or nuclear receptor that acts on DNA.

Whether a signalling ligand crosses the phospholipid bilayer determines whether it binds a transmembrane receptor or an intracellular receptor.

Feature Transmembrane receptor Intracellular receptor
Ligand Usually hydrophilic; remains outside Lipid-soluble, such as steroid hormones; crosses membrane
Location Spans plasma membrane Cytoplasm or nucleus
Amino-acid distribution Hydrophobic residues face membrane lipids; hydrophilic regions face extracellular fluid/cytosol Soluble receptor surface is mainly hydrophilic; ligand-binding pocket matches a hydrophobic ligand
Immediate effect Starts an intracellular relay Activated complex binds specific DNA sequences

Oestradiol, progesterone and testosterone cross the membrane and bind intracellular receptors. The activated hormone–receptor complex binds specific DNA sequences and promotes transcription of target genes.

Receptor location follows ligand permeability and protein structure, not simply whether the signal is called a hormone. Protein hormones generally require surface receptors; steroid hormones use intracellular receptors.

Transmembrane vs. intracellular receptors

HL only

Assessment in practice

3–6 marks
How it is assessed

This objective is assessed through structured response, commonly using Distinguish / Outline / Compare.

Command terms

Distinguish / Outline / Compare / Contrast / Explain / Describe

What earns marks

Build the answer around this relationship: Peptide hormones usually bind receptors on the plasma membrane.

Representative question

Question 1

[Maximum number: 6]

Compare and contrast the mode of action of peptide hormones and steroid hormones.

Chemical Signalling

HL only

A ligand only affects target cells with the matching receptor. Quorum sensing uses autoinducers and thresholds for group behaviour. Animal signals differ by source, distance, speed, target-cell response, and chemical class. Hydrophilic ligands use transmembrane receptors and relays; steroid and thyroid hormones use intracellular receptors that affect transcription. Named pathways then show the logic: acetylcholine opens sodium channels, GPCRs switch G proteins through GDP-GTP exchange, epinephrine uses cAMP and kinase cascades, insulin RTKs use dimerisation/autophosphorylation to move GLUT4 and promote glycogenesis, steroid hormones change gene expression, and feedback either amplifies or restores stability.

  • Start every signalling answer with ligand specificity and target-cell receptor matching.
  • Then choose the route: local synapse, blood-borne hormone, transmembrane receptor, or intracellular receptor.
  • For named mechanisms, give the sequence, not just the pathway name.
  • Finish feedback comparisons with amplification versus stability.

Concept essentials

  • Peptide hormones usually bind receptors on the plasma membrane.
  • Steroid hormones can cross membranes and bind intracellular receptors.
  • Peptide hormone signalling often uses second messengers and enzyme cascades.
  • Steroid hormone-receptor complexes can regulate transcription of specific genes.