The big idea: Not every signalling molecule has to knock on the door. Some go straight in.
A lipid-soluble signal — like a steroid hormone (e.g. testosterone, oestrogen, cortisol) or thyroxine — dissolves through the plasma membrane and enters the cell.
Once inside, it binds a receptor that is already in the cell — in the cytoplasm or the nucleus. These are called intracellular receptors.
The big payoff: the hormone-receptor pair then switches genes on or off, changing which proteins the cell makes.
- Lipid-soluble (hydrophobic) signal
- A signalling molecule that dissolves in fats/lipids, so it can pass straight through the lipid plasma membrane. Steroid hormones and thyroxine are examples.
- Intracellular receptor
- A receptor located INSIDE the cell — in the cytoplasm or nucleus — rather than on the surface. It can only be reached by a signal that crosses the membrane.
- Steroid hormone
- A lipid-soluble hormone made from cholesterol (e.g. testosterone, oestrogen, cortisol). It enters target cells directly.
- Hormone-receptor complex
- The unit formed when the hormone binds its intracellular receptor; this complex is what acts on the DNA.
- Transcription factor
- A protein that binds DNA and controls whether a gene is transcribed (switched on) or not.
Why 'lipid-soluble' is the whole trick: The plasma membrane is mostly lipid. Like dissolves like, so a lipid-soluble signal slips through it easily.
A water-soluble signal cannot — it has to stay outside and use a surface receptor instead (that's the other route, covered next).
So the solubility of the signal decides which kind of receptor it uses.
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Follow the intracellular route as a chain of cause and effect — each step makes the next one happen, ending in a change to gene expression.
The intracellular signalling pathway (step by step)
- A lipid-soluble hormone (steroid or thyroxine) diffuses through the plasma membrane into the cell.
- Inside, it binds an intracellular receptor in the cytoplasm or nucleus, forming a hormone-receptor complex.
- The complex moves to the DNA in the nucleus (if it wasn't already there).
- The complex acts as a transcription factor — it binds specific genes on the DNA.
- This switches those genes ON (or, for some genes, off) — transcription is started or stopped.
- The cell makes new mRNA and new proteins, so which proteins the cell produces changes — and the effect lasts.
| Step | What happens |
|---|---|
| 1. Diffuse in | The lipid-soluble hormone passes straight through the plasma membrane |
| 2. Bind receptor | It binds an intracellular receptor in the cytoplasm or nucleus |
| 3. Form a complex | Together they form a hormone-receptor complex |
| 4. Act as transcription factor | The complex binds to DNA at specific genes |
| 5. Switch genes on/off | Transcription of those genes is turned ON (or off) |
| 6. Change the proteins made | New mRNA → new proteins → the cell's behaviour changes, and the effect lasts |
The key move: a hormone that controls genes: The clever part is step 4. The hormone-receptor complex itself acts as a transcription factor.
By binding the DNA it decides whether a gene is read or not — so it controls gene expression directly.
Because the response is new protein synthesis, it takes a while to get going but then persists: the cell genuinely behaves differently.
Now meet the other route — the FAST one: Water-soluble signals (most peptide hormones, adrenaline) can't cross the membrane. They bind a surface receptor that spans the membrane.
The receptor then triggers a second messenger (e.g. cyclic AMP) inside the cell, which activates enzymes that already exist.
Result: a response that is fast to start but short-lived — it stops once the signal is gone. No new genes need to be switched on.
The OTHER route, for comparison — the FAST pathway. A water-soluble signal cannot cross the membrane, so it binds a receptor ON the cell surface; the receptor relays the signal to a second messenger inside, giving a fast, short-lived response. Intracellular receptors work the opposite way: the signal goes straight in.
Interactive diagram
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Slow-but-lasting vs fast-but-fleeting: Intracellular receptors → changes gene expression → slower to start, but longer-lasting.
Surface receptors + second messengers → switch on existing proteins → fast to start, but short-lived.
Same job (passing a signal into the cell), but two opposite trade-offs of speed vs duration.
| Intracellular receptors | Surface (membrane) receptors | |
|---|---|---|
| Signal type | LIPID-soluble (steroid hormones, thyroxine) | WATER-soluble (e.g. peptide hormones, adrenaline) |
| Crosses the membrane? | YES — it diffuses straight through the phospholipid bilayer | NO — it stays outside and binds a receptor in the membrane |
| Where the receptor is | INSIDE the cell — in the cytoplasm or nucleus | ON the cell surface — spanning the plasma membrane |
| How the message gets in | The hormone itself carries the message into the cell | A second messenger (e.g. cyclic AMP) relays it inside |
| What happens at the end | Hormone-receptor complex binds DNA and switches GENES on/off | A relay/cascade activates existing enzymes in the cytoplasm |
| Speed to START | SLOWER (making new proteins takes time) | FAST (existing proteins are switched on at once) |
| How LONG it lasts | LONGER-lasting (changes which proteins the cell makes) | SHORT-lived (stops when the signal is removed) |
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How this is tested: A favourite HL outline/explain question asks how a steroid hormone (or thyroxine) changes a target cell — score points for: lipid-soluble → diffuses through the membrane → binds an intracellular receptor → complex acts as a transcription factor → binds DNA → switches genes on/off → changes the proteins made.
A compare/distinguish question contrasts intracellular vs surface receptors — the marks live in the speed vs duration trade-off (slow but lasting vs fast but short-lived) and where the receptor is (inside vs on the surface).
Watch the trap: a steroid does not use a second messenger, and a water-soluble signal does not enter the cell.
IB-style question — how a steroid hormone changes a target cell
Cortisol is a steroid hormone. Explain how it changes the activity of a target cell, and state one way this differs from signalling by a water-soluble hormone. [6]
How to score all six marks
- Lipid-soluble → enters. Cortisol is lipid-soluble, so it diffuses straight through the plasma membrane into the cell.
- Binds an intracellular receptor. Inside, it binds a receptor in the cytoplasm/nucleus, forming a hormone-receptor complex.
- Acts as a transcription factor. The complex binds to DNA and acts as a transcription factor.
- Switches genes on/off. This switches specific genes ON (or off), changing transcription.
- Changes the proteins made. New mRNA → new proteins, so which proteins the cell makes changes — a slower but longer-lasting effect.
- The difference. A water-soluble hormone cannot cross the membrane; it binds a surface receptor and uses a second messenger to switch on existing proteins — a fast, short-lived response. (Award 1 mark per distinct point, up to 6.)
Final answer
Cortisol is lipid-soluble, so it diffuses through the plasma membrane and binds an intracellular receptor. The hormone-receptor complex acts as a transcription factor, binding DNA and switching specific genes on or off, which changes the proteins the cell makes (a slow, long-lasting effect). A water-soluble hormone instead binds a surface receptor and uses a second messenger to give a fast, short-lived response without entering the cell.
✓ Why this scores full marks: It tracks the whole intracellular chain (lipid-soluble → diffuses in → intracellular receptor → complex → transcription factor → genes on/off → new proteins) and nails the contrast the question asked for: surface receptor + second messenger = fast and short-lived.
A common way to lose marks is to say a steroid uses a second messenger — it does not. Second messengers belong to the surface-receptor route.
| Intracellular receptors | Surface (membrane) receptors | |
|---|---|---|
| Signal type | LIPID-soluble (steroid hormones, thyroxine) | WATER-soluble (e.g. peptide hormones, adrenaline) |
| Crosses the membrane? | YES — it diffuses straight through the phospholipid bilayer | NO — it stays outside and binds a receptor in the membrane |
| Where the receptor is | INSIDE the cell — in the cytoplasm or nucleus | ON the cell surface — spanning the plasma membrane |
| How the message gets in | The hormone itself carries the message into the cell | A second messenger (e.g. cyclic AMP) relays it inside |
| What happens at the end | Hormone-receptor complex binds DNA and switches GENES on/off | A relay/cascade activates existing enzymes in the cytoplasm |
| Speed to START | SLOWER (making new proteins takes time) | FAST (existing proteins are switched on at once) |
| How LONG it lasts | LONGER-lasting (changes which proteins the cell makes) | SHORT-lived (stops when the signal is removed) |