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INTRODUCTION

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OBJECTIVES

After studying this chapter, you should be able to:

  • Explain the roles of stimulus, hormone release, signal generation, and effector response in a variety of hormone-regulated physiological processes.

  • Explain the role of receptors and GTP-binding G proteins in hormone signal transduction, particularly with regard to the generation of second messengers.

  • Appreciate the complex patterns of signal transduction pathway cross-talk in mediating complicated physiological outputs.

  • Understand the key roles that protein-ligand, protein-protein, protein posttranslational modification (eg, phosphorylation and acetylation), and protein-DNA interactions play in mediating hormone-directed physiological processes.

  • Appreciate that hormone-modulated receptors, second messengers, and associated signaling molecules represent a rich source of potential drug target development given their key roles in the regulation of physiology.

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BIOMEDICAL IMPORTANCE

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The homeostatic adaptations an organism makes to a constantly changing environment are in large part accomplished through alterations of the activity and amount of proteins. Hormones provide a major means of facilitating these changes. A hormone-receptor interaction results in generation of an intracellular signal that can either regulate the activity of a select set of genes, thereby altering the amount of certain proteins in the target cell, or affect the activity of specific proteins, including enzymes and transporter or channel proteins. The signal can influence the location of proteins in the cell and can affect general processes such as protein synthesis, cell growth, and replication, often through effects on gene expression. Other signaling molecules—including cytokines, interleukins, growth factors, and metabolites—use some of the same general mechanisms and signal transduction pathways. Excessive, deficient, or inappropriate production and release of hormones and of these other regulatory molecules are major causes of disease. Many pharmacotherapeutic agents are aimed at correcting or otherwise influencing the pathways discussed in this chapter.

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HORMONES TRANSDUCE SIGNALS TO AFFECT HOMEOSTATIC MECHANISMS

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The general steps involved in producing a coordinated response to a particular stimulus are illustrated in Figure 42–1. The stimulus can be a challenge or a threat to the organism, to an organ, or to the integrity of a single cell within that organism. Recognition of the stimulus is the first step in the adaptive response. At the organismic level, this generally involves the nervous system and the special senses (sight, hearing, pain, smell, and touch). At the organ, tissue, or cellular level, recognition involves physicochemical factors such as pH, O2 tension, temperature, nutrient supply, noxious metabolites, and osmolarity. Appropriate recognition results in the release of one or more hormones that will govern generation of the necessary adaptive response. For purposes of this discussion, the hormones are categorized as described in Table 41–4, that is, based on the location of their specific cellular receptors and the type of signals generated. Group I hormones interact with an intracellular receptor and group II hormones with receptor recognition sites located on the extracellular surface of the plasma membrane of target cells. The cytokines, interleukins, and growth factors ...

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