IB Biology HLChemical SignallingPaper 1 & 2~12 min read
Intracellular Receptors
Some hormones do not stop at the door. They walk through the membrane, through the nuclear envelope, and end up sitting on the DNA itself — changing which genes a cell chooses to use. It is a slower kind of message, and a much longer lasting one.
📚 What you need to know
Eukaryotes use transcription factors to control gene expression. A transcription factor is a protein that controls transcription by binding to a specific region of DNA.
A gene is expressed if it is transcribed and translated.
Steroid hormones are small, hydrophobic and lipid-based, so they diffuse through the cell membrane and pass into the nucleus through nuclear pores.
Inside, they bind to intracellular receptors.
Steroid hormones such as testosterone, progesterone and oestradiol control the expression of many genes. Up to 100 different genes are controlled by oestradiol.
The oestradiol pathway: diffuses in, enters the nucleus, binds the ER-alpha receptor held in a protein complex, causes a conformational change, detaches, binds a cofactor, then binds the promoter region, stimulating RNA polymerase binding and transcription.
Oestradiol regulates female sexual characteristics and, with LH and FSH, the menstrual cycle. It can inhibit or promote GnRH release, giving positive or negative feedback.
Progesterone maintains the endometrial lining and prevents further ovulation during pregnancy.
Receptors that affect gene expression
A transcription factor is a protein that controls the transcription of genes by binding to a specific region of DNA. If a gene is transcribed and then translated, we say it is expressed in the cell or individual.
This is what makes intracellular receptors different from everything on the previous pages. A surface receptor usually changes what a cell is doing. An intracellular receptor changes what a cell is making.
Why steroids can do this and insulin cannot. Steroid hormones are small, hydrophobic and lipid-based. The middle of a membrane is also lipid, so a steroid dissolves straight through it, and then through a nuclear pore. A hydrophilic protein hormone is stopped at the first barrier and has to send a message instead.
The oestradiol stimulation pathway
Oestradiol (also known as oestrogen) helps control the female fertility cycle and also stimulates sperm production in males. Up to 100 different genes are controlled by it.
The green block on the DNA is the promoter region. Once the activated receptor is sitting there, RNA polymerase can bind and start reading the gene.
🧩 The five steps in full
Oestradiol diffuses through the cell surface membrane into the cytoplasm.
It diffuses through a nuclear pore into the nucleus.
In the nucleus it attaches to an ER-alpha oestradiol receptor that is held within a protein complex. This causes the receptor to undergo a conformational change.
The new shape allows the receptor to detach from the protein complex and diffuse towards the gene to be expressed.
The receptor binds to a cofactor, which enables it to bind to the promoter region of the gene. This stimulates RNA polymerase binding and gene transcription.
The examiner point here is that oestradiol is only an example. Progesterone and testosterone follow a similar path: bind to and activate an intracellular receptor, and the activated receptor then binds specific DNA sequences to stimulate transcription. If a question uses a steroid you have never met, describe this same route.
Oestradiol and progesterone
Oestradiol
A steroid hormone responsible for regulating female sexual characteristics, among other roles.
Produced in the ovaries, placenta and testes, but regulated by hormones released from the hypothalamus.
Gonadotropin releasing hormone (GnRH) is released first from the hypothalamus.
This stimulates release of luteinising hormone (LH) and follicle stimulating hormone (FSH) from the pituitary gland.
Together these control the menstrual cycle, with target cells in the uterus, breasts and bone marrow.
Oestradiol can either inhibit or promote GnRH release across the cycle, giving either a negative or a positive feedback response.
Most hormones only ever damp themselves down. Oestradiol is unusual because at one point in the cycle it does the opposite and pushes its own release higher.
Progesterone
A steroid hormone responsible for maintaining the endometrial lining, in preparation for implantation of a fertilised ovum and development of a foetus.
It also prevents further ovulation during pregnancy.
Produced by the corpus luteum and the placenta.
On entering the cytoplasm of a target cell, progesterone forms a ligand–receptor complex, leading to expression of a range of genes.
One example is a growth factor that promotes cell proliferation, needed to continuously replenish the endometrial cells of the uterus.
Hormone
Where it is made
Main role
Oestradiol
ovaries, placenta and testes
regulates female sexual characteristics and the menstrual cycle; controls up to 100 genes
Progesterone
corpus luteum and placenta
maintains the endometrial lining and prevents further ovulation during pregnancy
🔑
Surface or inside?
Ask one question: can it cross a membrane? If yes it is a steroid, it uses an intracellular receptor, and the response is a change in gene expression. If no, it uses a surface receptor, a second messenger and a cascade. That single question answers most of this topic.
Worked examples
WE 1
Describe the oestradiol pathway
Describe how oestradiol stimulates the transcription of a gene. (5 marks)
Step 1: getting in
Oestradiol is hydrophobic, so it diffuses through the cell surface membrane into the cytoplasm.
Step 2: into the nucleus
It diffuses through a nuclear pore into the nucleus.
Step 3: binding
It attaches to an ER-alpha receptor held in a protein complex, causing a conformational change.
Step 4: release
The new shape lets the receptor detach from the protein complex and diffuse towards the gene to be expressed.
Step 5: transcription
It binds a cofactor, which lets it bind the promoter region, stimulating RNA polymerase binding and gene transcription.
Diffuse in, bind, change shape, detach, bind promoter, transcribe“conformational change” and “promoter region” are both specific marking points — use the exact words
WE 2
Explain a difference in response time
Suggest why a response to a steroid hormone is usually slower to appear than a response to a neurotransmitter. (3 marks)
Point 1: what the steroid does
A steroid hormone changes gene expression, so the response depends on transcription and translation of a new protein.
Point 2: why that takes time
Making mRNA and then a protein takes far longer than opening an ion channel that is already in the membrane.
Point 3: the trade-off
In exchange, the effect lasts much longer, because the protein remains in the cell after the hormone has gone.
Building a protein is slow; opening a door is instant“suggest” questions want reasoning — finish with the trade-off to secure the third mark
WE 3
Explain the role of progesterone
Explain how progesterone maintains the endometrial lining of the uterus. (3 marks)
Point 1: entry and binding
Progesterone is a steroid, so it enters the cytoplasm of a target cell and forms a ligand-receptor complex.
Point 2: the effect on genes
This leads to the expression of a range of genes, including one coding for a growth factor.
Point 3: the outcome
The growth factor promotes cell proliferation, continuously replenishing the endometrial cells and so maintaining the lining for implantation.
Gene expression makes a growth factor, and the growth factor rebuilds the liningdo not stop at “it maintains the lining” — the marks are in the mechanism
💡 Exam tips
Define a transcription factor as a protein that controls transcription by binding to a specific DNA region.
Describe steroids as small, hydrophobic and lipid-based.
Learn the five oestradiol steps in order, including cofactor and promoter region.
Name the chain hypothalamus → GnRH → pituitary → LH and FSH → ovaries.
Note that oestradiol can give either negative or positive feedback.
If given an unfamiliar steroid, apply the same route: diffuse in, bind an intracellular receptor, change gene expression.
⚠ Common mistakes
Saying steroid hormones need a channel or carrier protein. They diffuse straight through the bilayer.
Saying oestradiol uses a second messenger. It does not — it reaches the DNA itself.
Confusing the promoter with the gene. The receptor binds the promoter; RNA polymerase then transcribes the gene.
Forgetting the protein complex. The receptor is held in one until the conformational change releases it.
Saying oestradiol is only produced in ovaries. The placenta and testes produce it too.
Saying steroid responses are fast. They are slower to appear but longer lasting.
Up next: Regulating Cell Signalling. Every signal in this topic has needed an off switch. In the last page of the topic we look at the two systems that decide when a signal should be shut down — and when it should be made even stronger.
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