Saturday, 24 March 2012

Mechanisms of Hormone Action

In this post I'll explain how steroid hormones, the adenylate cyclase mechanism, and how tyrosine kinase receptors work to cause a cell to produce certain proteins.

There are two broad classes of hormones, steroid hormones and peptide hormones. Steroid hormones are derived from cholesterol and so are lipid soluble. This allows them to diffuse through the cell membrane to bind to intracellular receptors resulting in changes in DNA transcription. Peptide hormones are composed primarily of amino acids which are not lipid soluble, thus they are unable to easily pass through the cell membrane. Instead, peptide hormones interact with membrane receptors and are coupled to signal transduction systems. Peptide hormones provide a fast mechanism of action while steroid hormones are slower.

Steroid Hormones 

Examples of steroid hormones include the sex hormones, glucocorticoids and mineralocorticoids. They are hydrophobic and so they require a carrier protein to travel in the blood plasma.

Mechanism of Action:

All steroid hormones have the same mechanism of action which is outlined as follows.The hormone diffuses through the cell membrane and binds to a cytoplasmic receptor (some travel to the nucleus to bind to the receptor). The hormone then enters the nucleus and he hormone-receptor complex binds to hormone response elements on the DNA. The hormone-receptor complex may stimulate or inhibit the transcription of a particular gene. If the complex stimulates transcription, the binding of the hormone-receptor complex activates the gene and mRNA is transcribed and moved to the cytoplasm where protein translation takes place. Because of all the steps involved the response is relatively slow. 

Peptide Hormones

Peptide hormones are hydrophillic and so can be transported in the blood stream easily. Examples of peptide hormones include: Growth Hormone, Prolactin and Oxytocin. Because peptide hormones cannot easily diffuse through the cell membrane they have to use a mechanism of action called the G-Protein mode of action. The binding of the hormone to a receptor located on the cell surface activates a G-protein which initiates the production of a "second messenger". The most common "second messengers" are cyclic AMP (cAMP), inositol triphosphate (IP3) and diacylglycerol (DAG). The second messenger initiates a series of intracellular events such as: the phosphorylation and activation of enzymes; or the release of Ca2+ stores within the cytoplasm.

The cAMP/Adenylate Cyclase Pathway

the pathway begins when the hormone binds to the receptor. Several steps then occur:
  1. The G-protein is activated causing it to exchange its bound GDP for GTP
  2. Activated G-proteins bind to adenylate cyclase
  3. Activated adenylate cyclase produces cAMP
  4. cAMP activates Protein Kinase A
  5. Protein Kinase A phosphorylates other proteins: this switches them on or off and causes a cascade of cellular events.
This process is shown in the video below.

An example of a hormone which uses this method of action is adrenaline. 

Tyrosine Kinase Associated Receptors

These types of receptors do not require G-proteins or enzymes to transfer the signal from the hormone because the receptors are themselves enzymes. When no hormone is bound the receptor exists as a monomer. The binding of a hormone causes the receptor to dimerise which initiates intracellular signalling. The receptor phosphorylates tyrosine residues on itself causing it to become active. The activated receptor then phosphorylates tyrosine residues on other proteins in the cytoplasm. Eventually the receptor is switched off by tyrosine phosphatases. 

And that's all for this post, if you have any questions please feel free to ask :)



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