Pathways Initiated by Intracellular Receptors

Most lipid-soluble messengers are hormones (to be described in Chapter 10)—steroid hormones, the thyroid hormones, and the steroid derivative, 1,25-dihydroxy-vitamin D3. Structurally these hormones are all closely related, and their receptors constitute the steroid-hormone receptor "superfamily." The receptors are in-tracellular and are inactive when no messenger is bound to them; the inactive receptors are mainly in the cell nucleus. (In a few cases, cytosolic receptors are involved, but we shall ignore this.) Receptor activation leads to altered rates of gene transcription, the sequence of events being as follows.

The messenger diffuses across the cell's plasma membrane and nuclear membrane to enter the nucleus and bind to the receptor there (Figure 7-12). The

Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition

Homeostatic Mechanisms and Cellular Communication CHAPTER SEVEN

Capillary

Binding protein in plasma

Lipid-soluble messenger

Plasma membrane

Capillary

Binding protein in plasma

Lipid-soluble messenger

Plasma membrane

Lipid Soluble Messenger

FIGURE 7-12

Mechanism of action of lipid-soluble messengers. This figure shows the receptor for these messengers as being in the nucleus. In some cases, the unbound receptor is in the cytosol rather than the nucleus, in which case the binding occurs there, and the messenger-receptor complex moves into the nucleus.

TABLE 7-4 Classification of Receptors Based on Their Locations and the Signal Transduction Pathways They Use

FIGURE 7-12

Mechanism of action of lipid-soluble messengers. This figure shows the receptor for these messengers as being in the nucleus. In some cases, the unbound receptor is in the cytosol rather than the nucleus, in which case the binding occurs there, and the messenger-receptor complex moves into the nucleus.

receptor, activated by the binding of hormone to it, then functions in the nucleus as a transcription factor, defined in Chapter 5 as any regulatory protein that directly influences gene transcription. The receptor binds to a specific sequence near a gene in DNA, termed a response element, and increases the rate of that gene's transcription into mRNA. The mRNA molecules formed enter the cytosol and direct the synthesis, on ribosomes, of the protein encoded by the gene. The result is an increase in cellular concentration of the protein or its rate of secretion, and this accounts for the cell's ultimate response to the messenger. For example, if the protein encoded by the gene is an enzyme, the cell's response is an increase in the rate of the reaction catalyzed by that enzyme.

Two other points should be mentioned. First, more than one gene may be subject to control by a single receptor type, and second, in some cases the transcription of the gene(s) is decreased by the activated receptor rather than increased.

1. INTRACELLULAR RECEPTORS (Figure 7-12) (for lipid-soluble messengers) Function in the nucleus as transcription factors to alter the rate of transcription of particular genes.

2. PLASMA-MEMBRANE RECEPTORS (Figure 7-13) (for lipid-insoluble messengers)

a. Receptors that themselves function as ion channels.

b. Receptors that themselves function as enzymes.

c. Receptors that are bound to and activate cytoplasmic JAK kinases.

d. Receptors that activate G proteins, which in turn act upon effector proteins—either ion channels or enzymes—in the plasma membrane.

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Essentials of Human Physiology

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