The role of the steroid hormone, oestrogen, in initiating transcription.

The idea

Oestrogen is a steroid hormone, so it is lipid-soluble and diffuses straight through the phospholipid bilayer of the cell-surface membrane rather than binding on the outside. Inside the cell it binds to a receptor site on an oestrogen receptor, which is part of a transcriptional factor held inactive in the cytoplasm. Binding changes the tertiary structure of the receptor, releasing an inhibitor molecule and activating the factor. The oestrogen-receptor complex then moves into the nucleus and binds to the promoter region of its target genes, where it stimulates RNA polymerase so that transcription begins. mRNA is produced, translated at ribosomes, and the resulting proteins drive processes such as cell division in breast tissue.

What earns the marks

• Oestrogen being lipid-soluble and diffusing through the cell-surface membrane.
• Oestrogen binding to a specific receptor on the transcriptional factor and changing its tertiary shape, activating it.
• The oestrogen-receptor complex entering the nucleus and binding to the promoter region.
• RNA polymerase being stimulated or activated, so the target gene is transcribed.
• One mark, for a drug question, for the drug binding the oestrogen receptor and preventing oestrogen binding, so no or fewer transcriptional factors bind the promoter.

Common mistakes and how to put them right

• Describing oestrogen binding its receptor as forming an enzyme-substrate complex or entering an active site, which is explicitly rejected.

• Saying oestrogen binds to a receptor on the outside of the cell-surface membrane, as a protein hormone would.

• Saying oestrogen itself binds to the promoter, when it is the activated receptor complex that does.

• Writing that the oestrogen-like drug 'kills the cancer cells' with no mention of receptors or transcription.

• Leaving out the shape change, so there is nothing to explain why the factor becomes active.

Exam tips

• Build the chain in order: lipid-soluble, diffuses in, binds receptor, shape change, into nucleus, promoter, RNA polymerase, transcription.
• In ER-positive breast cancer questions each of the three marks is a separate link - receptor binding, oestrogen blocked, fewer factors at the promoter.
• Name the receptor as a transcriptional factor if you can; mark schemes accept 'inactive transcriptional factor' for receptor.