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certain target cells respond to any given hormone. Most cells are targets for more than one hormone and many hormones target more than a single cell type. The molecular mechanisms that underlie signal reception and transduction are discussed in Chapter 2 and are considered in subsequent chapters in relation to the actions of specific hormones.

Whether or not a cell responds to a hormone depends on whether or not it has receptors for that hormone (see Chapter 2). However, it is important to recognize that the nature of the specific response elicited in a given target cell is determined by that cell rather than by the hormone. In fact, different cell types may respond to the same hormone in different ways. For example, the adrenal hormone cortisol stimulates net protein breakdown in skeletal muscle and net protein synthesis in liver. Cortisol activates the same receptor in muscle and liver to produce these divergent actions, but other hormones may produce their effects through different receptors expressed in different cells. Vascular smooth muscle cells and epithelial cells in the collecting ducts of renal tubules are targets for the posterior pituitary hormone vasopressin. When stimulated by vasopressin, arterioles contract, whereas collecting ducts increase their permeability to water. The Vi receptor in vascular smooth muscle and the V2 receptor in renal tubules couple to different intracellular signaling pathways as well as to different effector molecules (see Chapter 28).

Modulation of Responding Systems

Not all aspects of hormonal control are determined simply by how much hormone is secreted or even when a hormone is secreted. Receptivity of target tissues to hormonal stimulation is not constant and can be changed under a variety of circumstances. Receptivity of target tissues to hormonal stimulation can be expressed in terms of two separate, but related, aspects: sensitivity to stimulation and the capacity to respond. Sensitivity describes the acuity of a cell's ability to recognize a signal and to respond in proportion to the intensity of that signal. Sensitivity is often described in terms of the concentration of hormone needed to produce a halfmaximal response. The relationship between the magnitude of a hormonal response and the concentration of hormone that produces the response can be described by a sigmoidal curve (Fig. 8). An increase in sensitivity lowers the concentration of hormone needed to elicit a half-maximal response and produces a leftward shift of the dose-response curve. Conversely, a decrease in sensitivity increases the concentration of hormone needed to evoke the same response and thus results in a rightward shift in the dose-response curve. In the example shown in Fig. 8, we can assume that curve B

■ More Sensitive

Less Sensitive ■

■ More Sensitive

Less Sensitive ■

Half Maximum

Hormone Concentration (nM)

FIGURE 8 The relationship between concentration and response. Three levels of sensitivity are shown. Arrows indicate the concentration of hormone that produces a half-maximal response for each level of sensitivity. Note that hormone concentrations are expressed on a logarithmic scale.

Half Maximum

Hormone Concentration (nM)

FIGURE 8 The relationship between concentration and response. Three levels of sensitivity are shown. Arrows indicate the concentration of hormone that produces a half-maximal response for each level of sensitivity. Note that hormone concentrations are expressed on a logarithmic scale.

represents the basal sensitivity that may be increased (curve A) or decreased (curve C) in different physiologic or pathologic conditions. Changes in capacity to respond are illustrated in Fig. 9. In this case the maximum response may be increased (curve A) or decreased (curve C), but the sensitivity (i.e., the concentration of hormone needed to produce the half-maximal response) remains unchanged at 1 ng/mL.

One mechanism by which hormones adjust the sensitivity of target cells is by regulating the availability of hormone receptors. These changes are referred to as up-regulation or down-regulation. Hormone-receptor interactions depend on the likelihood that a molecule

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