Intracellular receptors

 

Estrogen has been the best studied of cell steroid hormone known to possess intracellular receptors. The mechanism by which steroid hormones cause the synthesis of protein or RNA is still not known but it ahs been suggested that the main action occurs in the nucleus. The following processes have been postulated on its target cell.

1.         Estrogen crosses the cell membrane to enter cell. It then interacts with specific receptor protein in the cytoplasm to form complexes.

2.         The complex undergoes some transformational change which allows it to enter the nucleus.

3.         Complex interacts with nucleus in such a way as to affect general gene expression (repression & derepression) thereby causing new forms of protein synthesis or arresting older forms. The target cell is now ready to function in a specific way.

Estrogen receptor has been identified as 8.6 fraction of cell sedimentation. It also has 67Aoas it stokes radius in the absence of Ca2+ sedimentation rate of 5.3 S is known to occur with a molecular weight of 120,000 dalton and a stoke radius of 94Ao at salt concentration lower than 0.2M KCl. Because the molecular weight of 8.6S fraction is 240,000 daltons, it was that two 5.3S  molecules generally associate to form 8.6 state. It is suggested that the physiological form of receptor in the cell is the dissociated form. In the presence of calcium 4.5S sedimentation rate with 35Ao stoke radius is got. This has a molecular weight of 60,000 dalton. The receptor isolated without Ca2+ is called the native receptor as opposed to the derived receptor got in the presence of Ca2+. It is believed that there is a transformation from the native to the derived receptor in order that nuclear translocation of the estrogen receptor complex can be achieved. This translocation is caused by a calcium dependent cytoplasmic factor known as the “Receptor – Transforming Factor”.  The following can then be schematically represented as the mode of action of Estrogen in the cell.

1)          E enters the cell through the cytoplasm

2)          E combines with 5.3S native receptor

3)                 Ca2+ RTF + 5.1 S-E – 4.5 S – E

4)                 4.5S – E then entered the nucleus and interacts with chromatin and alter gene expression

Receptors

 

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