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15. Beskrive hvordan steroid hormoner udøver deres effekt på genekspression og herunder hvordan steroid hormon receptoren virker
Devlin, s.907
Devlin, s.974-976; fig. 22.14

Hormone - any substance in an organism that carries a signal to generate some sort of alteration at the cellular level.

Depending on the place of action in the cell, hormones can be devided into two groups:

• Peptide hormones and amino-acid derived hormones - excert their effects on the cellular level, by binding to receptors located on the cell surface

• Steroid hormones - these hormones, being liposoluble, can go through the cell membrane, enter the cell and bind to receptors in the cytosol; or are transported through the hydrophillic enviroment of the cytosol and go through the nucleus membrane where they interact with nucleus receptors.

There are several ways in which steroid hormones affect gene expression, depending on where the steroid hormone receptor is located.

1. the receptor is located in the cytoplasm

step 1 - the hormone has to be disassociated from the circulating carrier-protein which borught it to the target cell

step 2 - difussion of the hormone through the cell membrane into the cytosol

step 3 - the steroid hormone receptor is found in the cytoplasm. It is called non-DNA binding cytoplasmatic receptor. It has to binding domains:

• hormone-binding domain

• DNA-binding domain

Under normal cicumstances, when the receptor is in its inactive form, meaning no steroid hormone is bound, the DNA-binding domain is associated with a heat-shock protein. The domain is therefore occupied and does not bind DNA, thus the name non-DNA binding cytoplasmatic receptor.

step 4 - activation. The binding of the steriod hormone causes a confirmational change in the structure of the receptor, which realeases the heat-shock protein and the DNA-binding domain is now free.

step 5 - the activated receptor has to be transported into the nucleus

step 6 - the DNA-binding domain searches the DNA for a high-affinity acceptor transactivation factor, which together with other transactivators allows for the starting of the RNA-polymerase and the stimulation of transcription.

step 7 - the newly synthethised mRNA molecules are transported into the cytoplasm where translation takes place. The newly synthethised proteins alter metabolism and function of the target cell.

2. the receptor is located in the nucleus

step 1 - the hormone has to be disassociated from the circulating carrier-protein which borught it to the target cell

step 2 - difussion of the hormone through the cell membrane into the cytosol

step 3 - the steroid hormone has to travel through the cytoplasm. Since the envoroment is hydrophillic and the steroid hormone is, of course, hyrophobic, a transport-protein may be required.

step 4 - the inactive steroid hormone receptor is lready located on the DNA in the nucleus. The binding of the steroid hormone can have several effects:

• it might cause the receptor to initiate search of a compatible DNA sequence (in case the receptor is located far away from the acceptor seqeuence of the DNA)

• it might cause "activation" of the receptor if it located on or near the activation site

This allows RNA polymese to bind to the target DNA-sequence

step 5 - the newly synthethised mRNA molecules are transported into the cytoplasm where translation takes place. The newly synthethised proteins alter metabolism and function of the target cell.

The principple of action of the nuclear receptors is less understood.

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