28 - Chapter 28 MECHANISMS OF HORMONE ACTION occupied by...

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Chapter 28 MECHANISMS OF HORMONE ACT ION A. The hormone receptor Some general characteristics of hormone action were introduced earlier, along with some broad categories of types of responses in the target tissues. Most hormone action can now be explained on the basis of what is known of the hormone receptors, so this section provides a fairly comprehensive overview of the receptor. The receptor serves as a chemical transducer that must be present in a tissue if that tissue is to be a target for the hormone of interest (the ligand). Next, the receptor provides selectivity in the response system because it may be capable of interacting with a single hormone molecule or, at most, a very limited array of hormones with similar actions. For example, receptors for growth hormone can be occupied by growth hormones and some placental lactogens, but not by any other type of protein hormone. Third, the receptor confers specificity ; that is, the nature of the response to a given hormone's stimulation. The catecholamines introduced earlier bring about quite distinct responses in different tissues, depending on the precise nature of the adrenoreceptor in each of those tissues. For example, catecholamines stimulate heart muscle but may either contract or relax vascular smooth muscle. Different adrenoreceptors and downstream signal transduction pathways dictate that the target tissues react to the same stimulus in quite different ways. Another aspect of specificity is to assure that the response is predictable, irrespective of how it is provoked. When steroid hormones were described, there were several examples of classes of steroid containing very weak and very potent members. The estrogen receptor (R E ), for example, can be occupied by the weak estrogen, estrone, or the more potent relative, estradiol-17 β , and both steroids bring about characteristic estrogen actions, because the receptor, not the specific ligand, dictates specificity of response. The same is true for a wide variety of molecules, synthetic and naturally occurring, that are able to be bound by and activate the R E . In contrast, other molecules can be bound by the R E yet they block, rather than activate it; these receptor antagonists block the downstream events in estrogen's action so they have great potential for pharmacologically manipulating biological events. An estrogen antagonist, TAMOXIFIN, is widely used in chemotherapy for cancers that are sensitive to estrogen. Many receptors are functionally coupled to enzyme systems that can provide great amplification within the response pathway. For example, some actions of catecholamines depend on the occupied adrenoreceptor being able to stimulate adenylyl cyclase (AC), the enzyme responsible for producing 3'5'-cAMP. The cyclase is located on the cytoplasmic face of the plasmalemma, in close proximity to the adrenoreceptor. A single catecholamine molecule occupies a single receptor at a
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28 - Chapter 28 MECHANISMS OF HORMONE ACTION occupied by...

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