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and continues to permit the detection and chemical characterization of minute quantities (nanograms or picograms) of new hormones and the characterization of the many receptors. Now in the 1990s we are experiencing the cellular and molecular biological era of endocrinology. With the advent of scanning electron microscopes and confocal microscopy with the capability for real time imaging of living cells, coupled with the application of the plethora of molecular biological procedures and manipulations, the science of endocrinology is flourishing. It is not clear how soon the apex will be realized. Thus, today we know of the existence of over 130 hormones (see Appendix A for a tabulation), and scientists are actively engaged in categorizing and defining the sphere of influence and molecular mode of action of each hormone. Undoubtedly there are still additional hormones waiting to be discovered.

The terms "endocrine" and "hormone" were both derived from the Greek, "endokrinein" and "horma-ein," respectively. The original use of hormone implied an agent that can excite or arouse; in the modern era a hormone is perceived to be a defined chemical entity that is secreted or produced by specific glands or cells and that acts as a chemical messenger or signal molecule. A hallmark of hormones is their potency. A typical concentration of hormone in the blood may be (1100) X 10~10 M. The term "endocrine" originally implied a glandular secretion of hormonal products; in the modern era it is appreciated that single cells or clusters of cells that are not anatomically definable as a gland can also secrete or produce hormones.

Finally, the cellular constitutent that is the immediate recipient of the "information unit" or message of a hormone is the receptor. The biochemical organization of receptors is diverse but each receptor is, in general, structurally organized so that it can specifically recognize and interact with its own cognate hormone (not unlike the lock and key model of the substrate-enzyme intermediate). Because of the low circulating concentrations of the hormones, the receptor must have a very efficient "capture" mechanism for its hormone. As a consequence of the receptor-hormone interaction (however transient it may be), signal transduction occurs and a specific biological response^) is generated within and, in some instances, around the target cell, i.e., the cell responds to the presence of the hormone. An overview of a traditional glandular secretion of a hormone and its transport through the bloodstream to a distal target organ is presented in Figure 1-1.

The objective of this book is to provide a status report on the field of human hormones, viewed in the light of our current understanding of cellular and subcellular architecture, as well as the molecular details of their mode of action.

We now realize that the domain of endocrinology has become a science of signaling or communication mechanisms involving substances in a much broader category than previously connoted by the term "endocrine hormones." Logically, any substance that operates at the cellular level, generated either externally or internally, which conveys to that cell a message to stop, start, or modulate a cellular process, will come under the perview of modern endocrinology. In recognition of this fact, we have preferred to entitle this book Hormones rather than Endocrinology, since the latter term refers to the limited category of substances operating over long distances within the organism.

This chapter presents the first principles of hormone action. These include a discussion of the structural and functional classification of hormones and a detailed presentation of current theories of mechanisms of hormone action at both the cellular and subcellular levels. The remaining chapters then focus on individual classical endocrine systems (posterior pituitary hormones, pancreatic hormones, Ca2+ regulatory hormones, etc.) or newer domains of hormone action that are essential to a comprehensive understanding of the domain of hormone action (e.g., prostaglandins, cancer, pineal hormones).

B. Classes of Hormone Molecules

Originally there were perceived to be three major classes of hormones based upon their chemical structure. These are the peptide and protein hormones, the steroid hormones, and the amino acid-related hormones. Examples of human hormones for these categories are given in Table 1-1 (and include examples from the endocrine, paracrine, autocrine, and neurotransmitter systems). As the discovery of new hormones continues, it is apparent that it is not feasible to categorize all hormones into precisely these three families; e.g., the prostaglandins are derived from fatty acids. Appendix A provides a tabulation of the «130 hormones known at the present time, and the trivial name, source, and principal biological action are listed for each hormone.

C. Classification of Hormonal Communication Systems

As stated earlier, hormones are chemical messengers that send a signal within a physiological system from point A to point B. There are four identifiable hormonal communication systems; each has a differ-

1. General Considerations of Hormones stimulus for cellular secretion .

receptor for secretion-Tj^S' stimulating hormone

Ca2+. from outside of cell

capillary second NUCLEUS messenger endocrine hormone endocrine hormone secretion by exocytosis,

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