Almost without exception, a hormone

Almost without exception, a hormone affects its target tissues by first forming a hormone­receptor complex. Formation of this complex alters the function of the receptor, and the activated receptor initiates the hor­ monal effects. To explain this process, let us give a few examples of the different types of interactions.

Ion Channel–Linked Receptors. Virtually all the neu­ rotransmitter substances, such as acetylcholine and nor­ epinephrine, combine with receptors in the postsynaptic membrane. This combination almost always causes a change in the structure of the receptor, usually opening or closing a channel for one or more ions. Some of these ion channel–linked receptors open (or close) channels for sodium ions, others for potassium ions, others for calcium ions, and so forth. The altered movement of these ions through the channels causes the subsequent effects on the postsynaptic cells. Although a few hormones may exert some of their actions through activation of ion channel receptors, most hormones that open or close ions chan­ nels do this indirectly by coupling with G protein–linked or enzyme­linked receptors, as discussed next.

G Protein–Linked Hormone Receptors. Many hor­ mones activate receptors that indirectly regulate the

activity of target proteins (e.g., enzymes or ion channels) by coupling with groups of cell membrane proteins called heterotrimeric guanosine triphosphate (GTP)-binding proteins (G proteins) (Figure 75-4). Of more than 1000 known G protein–coupled receptors, all have seven transmembrane segments that loop in and out of the cell membrane. Some parts of the receptor that protrude into the cell cytoplasm (especially the cytoplasmic tail of the receptor) are coupled to G proteins that include
three (i.e., trimeric) parts—the α, β, and γ subunits. When
the ligand (hormone) binds to the extracellular part of the receptor, a conformational change occurs in the receptor that activates the G proteins and induces intra­ cellular signals that either (1) open or close cell mem­ brane ion channels, (2) change the activity of an enzyme in the cytoplasm of the cell, or (3) activate gene transcription.
The trimeric G proteins are named for their ability to bind guanosine nucleotides. In their inactive state, the α, β, and γ subunits of G proteins form a complex that binds guanosine diphosphate (GDP) on the α subunit. When
the receptor is activated, it undergoes a conformational change that causes the GDP­bound trimeric G protein to associate with the cytoplasmic part of the receptor and to exchange GDP for GTP. Displacement of GDP by GTP
causes the α subunit to dissociate from the trimeric
complex and to associate with other intracellular signal­ ing proteins; these proteins, in turn, alter the activity of ion channels or intracellular enzymes such as adenylyl cyclase or phospholipase C, which alter cell function.
The signaling event is terminated when the hormone is removed and the α subunit inactivates itself by convert­ ing its bound GTP to GDP; then the α subunit once again combines with the β and γ subunits to form an inactive,
membrane­bound trimeric G protein. Additional details of G protein signaling are discussed in Chapter 46 and shown in Figure 46-7.