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Web Topic 5.1: Steroid Receptors Control Gene Expression

[Referenced on textbook p. 125]

Most steroid receptors are located inside cells. Steroids, being lipids, can easily pass through the fatty outer membrane (plasma membrane) of a target cell and enter its cytoplasm. This ability makes them very different from the highly water-soluble hormones, such as proteins and monoamines, which cannot enter cells and must therefore bind to receptors located on the outside of the target cell’s plasma membrane. When a steroid molecule binds to its receptor, the receptor undergoes a change in shape that allows it to bind to DNA within the cell nucleus, but only to specific DNA sequences called response elements (see Figure 1). A particular gene may possess a response element that recognizes the estrogen receptor, for example, while another gene may possess a response element that recognizes the androgen receptor. The entry of a steroid hormone into a cell (in sufficient concentrations) activates the collection of genes that carry response elements for that hormone’s receptors. The activity of these genes, in turn, modifies the cell's structure or function in some way.

Figure 1  Steroids influence gene expression.

From this description, you might conclude that a hormone such as testosterone would have the same effect on all cells that possess androgen receptors, since all cells in the body contain the same genes. However, each cell type in the body has its own control mechanisms that determine which genes, out of the entire suite of genes that possess a steroid response element, are able to respond to the presence of the steroid. In part, these mechanisms involve yet another class of molecules known as coactivators that regulate the interaction between steroid receptors and response elements (Giguere, 2011). Thus different tissues respond to steroids in different ways: cells in genital tissue may be stimulated to grow faster, cells in the brain may be stimulated to be more electrically active, and endocrine cells may be stimulated to secrete more hormones. In other words, sex steroids modify the behavior of a tissue within the range of options available to that particular tissue.

We should also mention that steroid hormones can affect target cells by other means than binding to the “classic” steroid receptors that control gene expression. They can also affect cellular processes more directly by binding to receptors in the plasma membranes of cells; these receptors influence metabolic processes directly, without involving gene expression. This is an area of active research.

References

Giguere, V. (2011). Steroid hormone receptor signaling. In R. A Bradshaw and E. A. Dennis, (Eds.), Regulation of organelle and cell compartment signaling. Academic Press.

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