Genomic Processes

The most common and established pathway for estrogen as it arrives at the target cell is to enter the cell by diffusion or in some cases by active uptake [8,9].

Fig. 1. Genomic estradiol action; RNA Poly = RNA polymerase; F = Fos; J = Jun

Subsequently, estrogen binds cytoplasmatic or nuclear ERs (see Fig. 1), which are members of a large superfamily of receptor proteins that share a similar configuration and functionality, and play an important role in cell differentiation, growth and metabolism [10-13].

After the ligand binds the receptor this complex forms a dimer and then binds to specific DNA sequences, called estrogen response elements (EREs), of a responsive gene. These estrogen-ER complexes are also thought to bind to other nuclear sites, called activator proteins (AP) and require the transcription factors Fos and Jun [14] (see Fig. 1). Binding of the estrogen-ER complex to DNA can alter the transcription of a gene by an RNA polymerase to produce messenger RNA (mRNA), which in turn is translated to the corresponding protein by the cytoplasmic ribosomes. The ligand-receptor complex activates, represses, or modifies the level of gene expression, causing a change in the levels of specific proteins, and, as a result, altering cell function, growth and/or differentiation [8-9,12]. After dissociation of estrogen from the receptor, or detachment of the complex from the DNA acceptor site, gene transcription will terminate. Estrogen may diffuse out of the cell and be metabolized in the liver to less or non-active forms, or bind once again to another receptor. Altogether, the effects of this genomic response are distinguished by a comparatively long latency and duration of action, on the scale of minutes to hours to days [15].

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