Hormones

Anthony W. Norman, Helen L. Henry

• Editore: Academic Press
• Anno: 2014
• ISBN:
  9780080919065
• Edizione: 3
• Argomento: Medicine
• Categoria: Endocrinology & Metabolism

The 3rd edition of Hormones offers a comprehensive treatment of the hormones of humans all viewed from the context of current theories of their action in the framework of our current understanding their physiological actions as well as their molecular structures, and those of their receptors. This new edition of Hormones is intended to be used by advanced undergraduates and graduate students in the biological sciences. It will also provide useful background information for first year medical students as they engage in studies which are increasingly problem-based rather than discipline-focused. As the field of endocrinology itself has expanded so much in the past two decades, the up to date presentation of the basics presented in this book will be a solid foundation on which more specialized considerations can be based.

New to this Edition: Hormones, 3rd Edition is organized with two introductory chapters followed by 15 chapters on selected topics of the molecular biology of the major endocrine systems operative in humans. Coverage, for the first time of the following hormones; ghrelin, oxyntomodulin, kisspeptin, adrenomedullin, FGF23, erythropoietin, VIP and extended coverage of NO. Coverage of the hypothalamus has been integrated with the anterior pituitary because of the intimate functional and relationship between the two. Consideration of the role of hormones in cancer has been integrated into the chapters on the relevant hormones. Each of these areas occupies a unique niche in our understanding of the biological world and is part of the universality of signaling systems and how they govern biological systems.

• Organized with two introductory chapters, followed by 15 chapters on selected topics of the molecular biology of the major human endocrine systems
• New full color format includes over 300 full color, completely redrawn images
• Companion web site will host all images from the book as PPT slides and.jpeg files
• All chapters have been completely updated and revitalized. Coverage of the hypothalamus has been integrated into the anterior pituitary chapter and coverage of the thymus has been eliminated and left to immunology textbooks
• Provides essential basics for advanced undergraduates and graduate students in the biological sciences, as well as first year medical students as they engage in studies which are increasingly problem-based rather than discipline-focused

Chapter 1

Hormones

An Introduction

The objective of this book is to provide a status report on the field of human hormones, viewed in the light of the current understanding of cellular and subcellular architecture, as well as the molecular details of their mode of action. In this first chapter, some of the first principles of hormone action are presented as a foundation for the more specific considerations of individual hormonal systems in the chapters that follow.

Keywords

Endocrinology; hormonal communication; hormone; hormone biosynthesis; hormone receptors

I Overview of Hormones

A Introduction

The term “hormone” is derived from the Greek hormon, the present participle of impel, or set in motion, an apt characterization of these potent molecules. “Endocrine” is also derived from the Greek: endo- for internal or within and krinein meaning separate. This term conveys the distance of the site of secretion from the site of action that characterized the systems, such as the pancreas, the thyroid, and the reproductive glands that were studied in the early days of endocrinology.

The cellular constituent that is the immediate recipient of the hormone is the receptor, an entity whose importance is now so dominant in the study of hormones that it is hard to imagine that the existence and nature of these molecules were not appreciated until the early 1970s. The biochemical organization of receptors is diverse but each receptor is structurally organized so that it can specifically recognize and interact with its hormone. 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(s) is generated within and, in some instances, around the target cell—i.e., the cell responds to the presence of the hormone.

The domain of endocrinology includes the study of how, in a higher organism, cell A communicates with cell B by sending a chemical messenger or hormone. A detailed understanding of a particular endocrine system includes an understanding of the following: (a) the anatomical description of cells A and B and their immediate environment, as well as the distance between A and B; (b) the chemical structure of the hormone(H); (c) the details of the biosynthesis of the hormone by cell A; (d) the mode of transfer of H from cell A to cell B; (e) the detailed mechanism by which cell B uses receptors to detect the presence of H; (f) how cell B transduces the presence of H to initiate and sustain a biological response; and (g) how cell B communicates via a feedback loop with cell A to indicate the adequate presence of the hormone.

The study of endocrinology over the past century has been dependent upon the scientific methodologies available to probe the various endocrine systems. Thus, in the interval 1900–1960, endocrinology was largely pursued at the physiological level. This resulted in the discovery of approximately 25 hormones. The time it took to achieve structural understanding of a hormone was usually inversely proportional to the size of the hormone. For example, the complete structure of thyroxine (molecular weight 770) was defined in 1926, while the sequence and structure of the small protein hormone insulin was not obtained until 1953 (amino acid sequence) and 1969 (three-dimensional structure).

The biochemical era of endocrinology began in approximately 1955–1960 and extends to the present time. The availability of radioactive isotopes of carbon (¹⁴C), hydrogen (³H), phosphorus (³²P), among others, coupled with advances in chemical methodology (chromatography, mass spectrometry, nuclear magnetic resonance spectroscopy (NMR), and X-ray crystallography), has led to the detection and chemical characterization of minute quantities (nanograms or picograms) of new hormones and the characterization of many receptors. Now we are experiencing the cellular and molecular biological era of endocrinology. We have an increased ability to visualize how molecules behave in cells, through fluorescent dye tagging, confocal microscopy, and other imaging advances. The sequencing and continuing analysis of the human genome has expanded our knowledge of the molecular players (hormones and receptors) and their evolutionary relationship to each other. The ability to generate mouse models with specific genetic attributes that can be expressed as a function of development stage or other variables helps to fine tune our functional understanding of hormonal processes. As is always the case in scientific inquiry, new information results in new questions, which leads to new techniques to answer them.

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. In this chapter some of the first principles of hormone action are presented as a foundation for the more specific considerations of individual hormonal systems in the chapters to follow.

B Review of Animal Cell Structure

In order to describe the details of the synthesis of hormones and their interactions with target cells in the chapters to follow, it is appropriate to present a brief review of cellular organization. A typical animal cell is shown in Figure 1-1.

Figure 1-1 Structural elements of animal cells.
The major features shared by animal cells are shown. In eukaryotes the nuclear membrane separates the genetic material, the chromatin, from the cytoplasm. Molecules move between the two compartments through nuclear pores and a portion of the chromatin (see Figure 1-2), the nucleolus, is dedicated to the continual production of ribosomes. The cytoplasmic organelles depicted include the smooth endoplasmic reticulum (the microsomes of fractionated cells), which carries out metabolic conversions of carbohydrates and lipids, and the rough endoplasmic reticulum, associated with ribosomes that are synthesizing proteins to be secreted by the cell. These proteins are collected and processed in the Golgi apparatus. Mitochondria generate energy for the cell’s function from the products of the metabolism of carbohydrates, fats, and proteins. Peroxisomes and lysosomes degrade molecules that are no longer needed or are potentially harmful. Elements of the cell’s cytoskeleton are shown, including the centriole, part of the organizing center for microtubules. The plasma membrane is described in Figure 1-3.

1 Nuclear Organization

In eukaryotes, the nucleus, containing the chromatin, and the cytoplasm are separated, except during interphase of mitosis. The nuclear envelope, consisting of two membranes separated by a small space, is perforated by nuclear pores through which transport of macromolecules, proteins, and RNA, between the two major compartments of the cell, takes place. For example, messenger and transfer RNA as well as ribosomal subunits must move from the nucleus to the cytoplasm and proteins that participate in the synthesis, repair, and transcription of DNA must move into the nucleus from the cytoplasm. The latter include the steroid hormone receptors and other proteins that regulate gene transcription that will be discussed in the following chapters.

Figure 1-2A shows the fundamental organization of DNA, beginning with the structure of the double helix in the top panel. This is the form in which DNA is found except when it is being transcribed or replicated, at which times the two strands of the double helix are separated. Inside the nucleus is the nucleolus where the DNA encoding ribosomal RNA is continually being transcribed. The remainder of the DNA in the eukaryotic nucleus is present in a more tightly packed form, arising from an association between the DNA (with its negatively charged sugar-phosphate backbone) and basic, positively charged proteins called histones; the final step in making DNA accessible for transcription involves modification of histone proteins (acetylation) to loosen their association with the DNA. Further steps in the coiling and compaction of DNA are illustrated in Figure 1-2B. The result of this process is the packing of a linear molecule of DNA that is about 10⁵ μM long into a nucleus with a diameter of about 10 μM.

Figure 1-2 Organization of DNA.
A. Double helical DNA. The chemical nature of the DNA double helix is shown for a stretch of four base pairs. The negatively charged sugar-phosphate backbone is shown in yellow. Each purine, adenine (A, orange), or guanine (G, red) pairs with a pyrimidine, thymine (T, blue) or cytosine (C, green), respectively. The two DNA strands are complementary and anti-parallel to one another. The double helical structure of DNA is stabilized by the hydrogen bonds between the bases on each strand, two for each AT base pair and three for each GC base pair as well as by interactions between the stacked bases in the interior of the helix. B. Organization of DNA in chromosomes. The compaction of double helical DNA into a chromatid of a chromosome is shown. The first step is the coiling of the double helix of DNA around a core of histone proteins to form the core nucleosome. Histone H1 joins these “beads on a string,” 11 nm across, to promote their coiling upon themselves to form a 30 nm fiber. Further structural details are not completely understood, but include 300 nm loops and further coiling of these into the 700 nm chromatid.

2 The Plasma Membrane

Although the precise content of substances tha...