Steroid versus peptide hormones: receptors and mechanism of action
Fat-soluble steroid hormones act on receptors inside the cell to change gene transcription, whereas water-soluble peptide hormones act on receptors on the cell surface.
Remember
Steroid hormones are made on demand and act on intracellular receptors (receptors that sit in the cytoplasm or nucleus) to change gene transcription, so they are usually slower but longer-lasting than peptide hormones. Peptide hormones are stored in vesicles and act on cell-surface receptors, often through a second messenger (a small molecule that carries the signal on inside the cell).
Memory aid
Fat-soluble hormones walk through the membrane and work inside, whereas water-soluble hormones knock on the surface and send a messenger in.
Fat-soluble hormones pass through the membrane and work inside the cell, while water-soluble hormones stay at the surface and send a messenger in.
Hormones reach their effects by different routes, depending on whether they are fat-soluble or water-soluble. A steroid hormone, such as cortisol, is made on demand from cholesterol. Steroid-producing tissues do not normally store ready-made hormone, only cholesterol.
Steroids are lipophilic (fat-soluble), so they slip across the phospholipid bilayer (the oily double layer of the cell membrane) and bind an intracellular receptor, which sits in the cytoplasm or nucleus. The hormone-receptor complex then regulates gene transcription, which is the copying of a gene into messenger RNA, a working copy that the cell reads to build a protein. New proteins have to be made before the effect appears, so the response is usually slower, and it is lost when protein synthesis is blocked.
A peptide hormone is the opposite. It is hydrophilic (water-soluble), is kept in vesicles (small membrane-bound packages) until release, and does not readily cross the membrane. It binds a cell-surface receptor, often with a second messenger (a small molecule such as cyclic AMP that relays the signal inside the cell). Glucagon binds a G-protein coupled receptor (a surface receptor coupled to a G protein, a molecular switch just inside the membrane), which raises cyclic AMP (cAMP). That acts on proteins already in the cell, so the response can be fast.
Most hormones made from amino acids are water-soluble and bind surface receptors, but thyroid hormones are an exception: although made from the amino acid tyrosine, they are lipid-soluble, so T3 (triiodothyronine) works mainly through receptors in the nucleus. Insulin is another cAMP exception. It is a polypeptide stored in vesicles, but its receptor is a tyrosine kinase receptor (a receptor in the plasma membrane that adds phosphate groups to proteins), which triggers a protein phosphorylation cascade (a chain of proteins that are switched on as phosphate groups are added).
Key facts
- Steroid hormones
- are lipophilic and made from cholesterol when needed, not normally stored as finished hormone, and they act through receptors inside the cell to change gene transcription.
- Peptide hormones
- are water-soluble, are stored in vesicles before release and bind receptors on the cell surface.
- Speed
- new proteins have to be built, so the gene route is usually slower than surface signalling, and for cortisol the onset is often delayed by several hours.
- Second messenger
- glucagon and TSH (thyroid-stimulating hormone) bind G-protein coupled receptors, with cAMP as a second messenger.
- Insulin exception
- insulin uses a tyrosine kinase receptor, which starts a protein phosphorylation cascade.
- Thyroid hormone exception
- T3 is made from tyrosine yet is lipid-soluble, so it acts mainly through a receptor in the nucleus.
- Thyroid storage
- unlike steroid-producing tissues, which do not normally store finished hormone, the thyroid stores its hormones outside the cell.
Exam traps
- Steroid hormones are not stored in vesicles as ready-made steroid, because steroid-producing tissues do not normally store any finished hormone, only cholesterol.
- Being made from the amino acid tyrosine does not make a hormone use a tyrosine kinase receptor: the shared word is a coincidence, since T3 binds nuclear receptors, while tyrosine kinase receptors such as the insulin receptor start phosphorylation cascades.
- Insulin is stored in vesicles and acts at the cell surface, yet its receptor is a tyrosine kinase receptor that starts a protein phosphorylation cascade, not a G-protein coupled receptor.
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