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8.3: Nuclear Hormone Receptors

Another type of relatively simple, though much slower, signaling is seen in pathways in which the signals are steroid hormones, like estrogen or testosterone, pictured below. Steroid hormones, as you are aware, are related to cholesterol, and as hydrophobic molecules, they are able to cross the cell membrane by themselves. This is unusual, as most signals coming to cells are incapable of crossing the plasma membrane, and thus, must have cell surface receptors.

Figure 8.3.1: Estradiol and Testosterone

By contrast, steroid hormones have receptors inside the cell (intracellular receptors). Steroid hormone receptors are proteins that belong in a family known as the nuclear receptors.

Nuclear hormone receptors are proteins with a double life: they are actually dormant transcription regulators. In the absence of signal, these receptors are in the cytoplasm, complexed with other proteins (HSP in the figure on the following page) and inactive. When a steroid hormone enters the cell, the nuclear hormone receptor binds the hormone and dissociates from the HSP. The receptors, then, with the hormone bound, translocate into the nucleus.

In the nucleus, they regulate the transcription of target genes by binding to their regulatory sequences (labeled HRE for hormone- response elements). The binding of the hormone-receptor complex to the regulatory elements of hormone-responsive genes modulates their expression. Because these responses involve gene expression, they are relatively slow. Most other signaling pathways, besides the two we have just discussed, involve multiple steps in which the original signal is passed on and amplified through a number of intermediate steps, before the cell responds to the signal.

Figure 8.3.2: Steroid hormones act by modulating expression of hormone-responsive genes

We will now consider two signaling pathways, each mediated by a major class of cell surface receptor- the G-protein coupled receptors (GPCRs) and the receptor tyrosine kinases (RTKs). While the specific details of the signaling pathways that follow the binding of signals to each of these receptor types are different, it is easier to learn them when you can see what the pathways have in common, namely, interaction of the signal with a receptor, followed by relaying the signal through a variable number of intermediate molecules, with the last of these molecules interacting with target protein(s) to modify their activity in the cell.