Vitamins and Hormones (eBook)

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2005 | 1. Auflage
451 Seiten
Elsevier Science (Verlag)
978-0-08-045804-5 (ISBN)

Infos

First published in 1943, VITAMINS AND HORMONES is the longest-running serial published by Academic Press. In the early days of the Serial, the subjects of vitamins and hormones were quite distinct. The Editorial Board now reflects expertise in the field of hormone action, vitamin action, X-ray crystal structure, physiology, and enzyme mechanisms. Under the capable and qualified editorial leadership of Dr. Gerald Litwack, VITAMINS AND HORMONES continues to publish cutting-edge reviews of interest to endocrinologists, biochemists, nutritionists, pharmacologists, cell biologists, and molecular biologists. Others interested in the structure and function of biologically active molecules like hormones and vitamins will, as always, turn to this series for comprehensive reviews by leading contributors to this and related disciplines.

* First published in 1943, Vitamins and Hormones is AP's longest running serial
* Each volume contains cutting edge reviews by leading contributors

Inhalt

Cover 
1 
table of contents 6
Contributors 13
Preface 17
1. Extrapituitary Effects of the Growth Hormone-Releasing Hormone 18
I. INTRODUCTION 1 19
II. ENDOCRINE ROLE OF GHRH IN CARCINOGENESIS 
21 
III. VARIOUS CANCERS AND NORMAL TISSUES THAT PRODUCE AND RESPOND TO GHRH 22
IV. DIRECT EFFECTS OF GHRH 24
IN CARCINOGENESIS 24
V. MECHANISM OF ACTION FOR LOCALLY PRODUCED GHRH 30
VI. CONCLUSIONS AND PERSPECTIVES 33
ACKNOWLEDGMENTS 1 36
REFERENCES 1 36
2. IRS-1 and Vascular Complications in Diabetes Mellitus 42
I. INTRODUCTION 2 43
II. INSULIN RECEPTOR SUPERFAMILY 44
III. INSULIN RECEPTOR SUBSTRATES 46
IV. SIGNALING PATHWAYS REGULATED BY IRS-1 50
V. IRS-1 AND INSULIN RESISTANCE 59
VI. THE ROLE OF IRS-1 IN ATHEROTHROMBOTIC COMPLICATIONS 63
VII. SUMMARY AND FUTURE PERSPECTIVES 68
APPENDIX 2 69
ACKNOWLEDGMENTS 2 70
REFERENCES 2 70
3. Structural and Functional Properties of CCN Proteins 85
I. DISCOVERY OF THE CCN GENE FAMILY 86
II. CCN FAMILY MODULAR STRUCTURE 88
III. CCN FAMILY AND HEPARIN INTERACTIONS 90
IV. CCN GENE FAMILY AND INTEGRINS 91
V. CCN2 BINDING TO LRP 93
VI. CCN GENE FAMILY AND INTRACELLULAR SIGNALING 93
VII. THE LINK BETWEEN TGF-AND CCN2 94
VIII. CCN GENE FAMILY ACTION IN NORMAL BIOLOGICAL PROCESSES 96
IX. CCN PROTEIN ACTION IN PATHOLOGICAL DISEASE PROCESSES 101
X. SUMMARY 107
ACKNOWLEDGMENTS 3 107
REFERENCES 3 108
4. Stanniocalcin: No Longer Just a Fish Tale 120
I. GENERAL INTRODUCTION 4 121
II. EARLY STUDIES ON THE DISCOVERY AND FUNCTION OF STANNIOCALCIN IN FISH 
122 
III. THE DISCOVERY OF MAMMALIAN STANNIOCALCIN 124
IV. THE SEQUESTERING HYPOTHESIS 133
V. FUTURE DIRECTIONS 142
ACKNOWLEDGMENTS 4 144
REFERENCES 4 145
5. Thyroid Hormone Transporters 151
I. INTRODUCTION 5 152
II. THYROID HORMONE TRANSPORTERS 155
III. CONCLUSIONS 5 176
REFERENCES 5 177
6. Phytoestrogens and Colorectal Cancer Prevention 182
I. INTRODUCTION 6 183
II. PHYTOESTROGENS 184
III. EXPERIMENTAL STUDIES 187
IV. CONCLUDING REMARKS 203
ACKNOWLEDGMENTS 6 204
REFERENCES 6 204
7. Transcriptional Activities of Retinoic Acid Receptors 212
I. INTRODUCTION 7 213
II. RETINOID PHYSIOLOGY 214
III. RETINOID-BINDING PROTEINS 216
IV. TRANSCRIPTIONAL REGULATION BY RETINOIC ACID RECEPTORS: THE TRANSACTIVATION PROCESS 220
V. TRANSCRIPTIONAL REGULATION BY RETINOIC ACID RECEPTORS: THE TRANSREPRESSION PROCESS 247
VI. NONGENOMIC EFFECTS OF RETINOIDS 252
VII. CONCLUSION 7 253
REFERENCES 7 253
8. Biochemical and Ionic Signaling Mechanismsfor ACTH-Stimulated Cortisol Production 278
I. INTRODUCTION 8 279
II. ACTH RECEPTORS: cAMP- AND CA2+ DEPENDENT SIGNALING 280
III. IONIC MECHANISMS IN ACTH-STIMULATED CORTISOL SECRETION 282
IV. CHRONIC CONTROL OF ION CHANNEL EXPRESSION BY ACTH IN AZF CELLS 286
V. SUMMARY AND PROSPECTS 8 287
REFERENCES 8 289
9. ATP-Dependent Chromatin Remodeling Complexes and Their Role in Nuclear Receptor-Dependent Transcription In Vivo 293
I. INTRODUCTION 9 294
II. ATP-DEPENDENT CHROMATIN REMODELING COMPLEXES 299
III. ATP-DEPENDENT CHROMATIN REMODELING COMPLEXES AND THEIR ROLE IN NUCLEAR RECEPTOR-MEDIATED TRANSCRIPTION 303
IV. CONCLUSIONS 9 310
REFERENCES 9 311
10. Novel Roles for Acylation Stimulating Protein/C3adesArg: A Review of Recent In Vitro and In Vivo Evidence 320
I. INTRODUCTION 10 321
II. ASP PRODUCTION 322
III. ASP FUNCTION AND ROLE IN METABOLISM 323
IV. ASP EFFECTS ON INSULIN, CYTOKINE, AND PITUITARY HORMONE SECRETION 335
V. DISCUSSION 337
ACKNOWLEDGMENTS 10 338
APPENDIX: ABBREVIATIONS 10 338
REFERENCES 10 339
11. STAT3 and Transactivation of Steroid Hormone Receptors 344
I. INTRODUCTION 11 344
II. STAT STRUCTURE 345
III. MECHANISMS OF STAT ACTIVATION AND REGULATION 348
IV. THE JAK/STAT PATHWAY IN NONMAMMALIAN SYSTEMS 355
V. STATS IN HUMAN MALIGNANCY 357
VI. STAT3 AND STEROID HORMONE RECEPTOR ACTIVATION 359
VII. CONCLUSION 11 361
REFERENCES 11 361
12. Coactivators in Gene Regulation by STAT5 369
I. SIGNAL TRANSDUCTION BY STAT5 370
II. PHYSIOLOGICAL ROLE OF STAT5 373
III. STRUCTURE AND DNA-BINDING OF STAT5 374
IV. TRANSCRIPTIONAL ACTIVATION BY STAT5 376
V. INTERACTION OF STAT5 WITH OTHER SIGNALING PATHWAYS 384
VI. REGULATION OF STAT5 TRANSCRIPTIONAL ACTIVITY BY SECONDARY MODIFICATIONS 386
VII. CONCLUSIONS 12 388
REFERENCES 12 388
13. New Insights into the Regulation of Mammalian Sex Determination and Male Sex Differentiation 397
I. INTRODUCTION 13 398
II. THE GENETICS OF MALE SEX DETERMINATION 399
III. HORMONAL REGULATION OF MALE SEX DIFFERENTIATION 404
IV. CONCLUSION 13 414
REFERENCES 13 415
14. The Role of Alcohol and Steroid Hormones in Human Aggression 424
I. INTRODUCTION 14 425
II. ALCOHOL 426
III. THE ENDOCRINOLOGY OF AGGRESSION 428
IV. THE EFFECT OF ALCOHOL ON STEROID HORMONES 435
V. CONCLUSIONS 14 436
REFERENCES 14 438
Index 447

Textauszug

1

Extrapituitary Effects of the Growth Hormone-Releasing Hormone

Hippokratis Kiaris∗; Andrew V. Schally†; Anastasios Kalofoutis∗    ∗ Department of Biological Chemistry, Medical School, University of Athens 115 27 Athens, Greece
† Endocrine Polypeptide and Cancer Institute, VA Medical Center & Section of Experimental Medicine, Tulane University Medical Center New Orleans, Louisiana 70112, USA

Abstract

Growth hormone-releasing hormone (GHRH) is a neuropeptide secreted by the hypothalamus that stimulates the synthesis and release of growth hormone (GH) in the pituitary. Accumulating evidence suggests that in addition to GHRH's neuroendocrine action, GHRH is present in several extrahypothalamic tissues and is involved in a variety of cellular processes. Its function is related to the regulation of cell proliferation and differentiation of various nonpituitary cell types. In certain cases, ectopic production of GHRH has also been implicated in carcinogenesis. The mechanisms by which GHRH affects the peripheral extrapituitary tissues remain poorly understood, but it is likely that classic neuroendocrine action as well as paracrine and autocrine pathways are involved. Some headway has been made in the identification of extrapituitary receptors for GHRH and cDNA as splice variants of these GHRH receptors found in various tumors. The fact that the nonpituitary GHRH receptors are not fully identified, however, remains the major obstacle in studying, at a more mechanistic level, the action of local GHRH. This review summarizes the information available regarding the role of GHRH in the extrapituitary tissues with emphasis on its potential therapeutic and diagnostic applications.

I Introduction

Growth hormone-releasing hormone (GHRH) is secreted by the hypothalamus; after binding to specific GHRH receptors in the pituitary, GHRH induces the secretion and release of growth hormone (GH) (Krulich et al., 1968; Schally and Comaru-Schally, 1998; Schally et al., 1965). GH in turn stimulates the production of insulin-like growth factor-1 (IGF-1 predominantly in the liver, which is a mitogen-stimulating cell cycle progression and a survival factor/inhibitor of apoptosis for various cell types (Koutsilieris et al., 2001, 2000, 1999; Mitsiades and Koutsilieris, 2001; Reyes-Moreno et al., 1998; Schally and Varga, 1999). Several molecular forms of biologically active GHRH have been isolated from various sources, including pancreatic tumors and the hypothalamus in humans and animals (Guillemin et al., 1982, 1984; Ling et al., 1984; Rivier et al., 1982). Most of the biologically active forms of GHRH isolated from hypothalami and extrapituitary tissues and cancers contain 40 to 44 amino acids, corresponding to peptides of about 5.2 kD. These forms of GHRH have been shown to correspond to peptides resulting from the extensive and complex proteolytic cleavage to which pre-pro-GHRH (12.3 kD) is subjected following translation of its mRNA (Dey et al., 2004). This proteolytic processing has been shown to be mediated predominantly by furin at the N-terminal cleavage site followed by PC1/3 at the C terminus (Dey et al., 2004). The precise biological function of each pre-pro-GHRH–derived peptide as well as potential differences in the various peptide properties remain unclear. Whereas mature GHRH represents the peptide to which the well-characterized biological function (i.e., the stimulation of GH release) has been attributed, other products of pre-pro-GHRH processing are thought to possess some, yet clear, biological activity. One of these peptides, which has been designated GHRH-related peptide (GHRH-RP), has been shown to exert some effects in nonpituitary tissues by a mechanism involving the stem cell factor (SCF), with a potential role in blood cell development (Fang et al., 2000). Virtually full intrinsic biological activity is present in the 29 N-terminal amino acid residues [GHRH(1–29)NH2] which serves as the core for the development of potent agonistic and antagonistic analogs of GHRH (Rivier et al., 1982).

Despite the fact that the source for the initial isolation and characterization of GHRH was nonhypothalamic tumor tissue, namely pancreatic islet tumors with neuroendocrine properties (Frohman and Szabo, 1981; Guillemin et al., 1982; Rivier et al., 1982), and not the hypothalamus, little attention has been given to the potential role of this neuropeptide in carcinogenesis, probably with the exception of the role of GHRH in the development of pituitary tumors. An avalanche of research has instead focused on the endocrine system, including systemic effects of GHRH in the regulation of GH production and secretion and regulation of IGF-1, which together constitute the GHRH/GH/IGF-1 axis. Until research in the 1990, the direct effects of GHRH in carcinogenesis were ignored. Two lines of evidence point to a direct role of GHRH in the initiation, growth, as well as maintenance of nonpituitary malignant tumors. The first line of evidence is the pattern of expression of GHRH: besides the identification of the hypothalamus as the predominant source for the expression of GHRH, this neuropeptide has been recently detected in many types of nonpituitary tumors as well as some normal tissues (Bagnato et al., 1992, 1991; Berry and Pescovitz, 1998; Ciampani et al., 1992; Gaylinn, 1999; Kahan et al., 2000; Khorram et al., 2001a,b; Margioris et al., 1990; Moretti et al., 1990a,b; Stephanou et al., 1991). GHRH's relatively wide pattern of expression, wider than initially thought, implies functions for GHRH independent of the regulation of GH production because the pituitary is the only tissue in which a causative association between GH release and GHRH stimulation has been demonstrated. The second and equally important line of evidence is provided by the inhibition of GHRH action by antagonists of GHRH in vitro in cancer cells, in which by definition the endocrine GHRH/GH/IGF-1 axis is not operational (Csernus et al., 1999; Kiaris et al., 1999; Rekasi et al., 2000b). These GHRH antagonists strongly inhibit cell proliferation, suggesting that GH release is not necessary for manifestation of biological activities of GHRH. It has to be mentioned, however, that a causative relationship between the proliferation of the pituitary somatotrophs and the expression of GHRH has been established in experiments using transgenic and mutant animals. For example, overexpression of GHRH in mice results in pituitary hyperplasia due to the hyperproliferation of the somatotrophs, whereas the inhibition of the expression (GSH-1 deficient) or normal action (in little mice or dwarf rats) of GHRH produces the opposite phenotype exemplified by reduced proliferation of the pituitary somatotrophs (Downs and Frohman, 1991; Frohman and Kineman, 2002a, 2000b; Hammer et al., 1985; Mayo et al., 2000; Mutsuga et al., 2001; Tierney and Robinson, 2002). In those studies, however, the effects of GHRH were closely linked with the stimulation of the pituitary GHRH receptor.

The authors of this review have tried to summarize the available information associating GHRH with carcinogenesis in nonpituitary tissues with special emphasis on the autocrine//paracrine stimulatory signals that appear to operate in tumors. This review will not discuss the role of GHRH in pituitary tumors, although well described in both human specimens as well as in transgenic animals (Hammer et al., 1985; Losa and Werder, 1997), because the topic remains outside the discussion's scope. Instead, this chapter focuses on the extrapituitary effects of the neuropeptide.

II Endocrine Role of GHRH in Carcinogenesis

Considering that IGF-1 has been causatively associated with carcinogenesis (Furstenberger and Senn, 2002; Hadsell and Abdel-Fattah, 2001) and that GHRH affects IGF-1 production through stimulation of GH secretion, it is conceivable for GHRH to induce the growth of IGF-1-dependent tumors. Indeed, this hypothesis has been tested by early studies in mice more than a decade ago, which indicated that hypophysectomy, which surgically disrupts the normal secretion of GH and subsequently the production of IGF-1 inhibits the growth of osteosarcomas that are highly dependent on IGF-1 (Pollak et al., 1992). Subsequent studies, which involved little (lit/lit) mice that are deficient in GH production due to a missense mutation in the GHRH receptor, confirmed these findings and underlined the role of GHRH in tumor development through secondary regulation of IGF-1 (Bugni et al., 2001; Deitel et al., 2002). Additional experiments using these animals demonstrated that genetic ablation of GHRH action results in reduced sensitivity to chemically induced liver carcinogenesis. Furthermore, the same type of animal was shown to provide a nonpermissive environment for the growth of established breast tumors, as compared to wild-type animals (Yang et al., 1996). Inoculation of...

Produkt-Details

• Erscheint lt. Verlag: 18.3.2005
• Mitarbeit: Chef-Herausgeber: Gerald Litwack
• Sprache: englisch
• Themenwelt: Medizinische Fachgebiete ► Innere Medizin ► Endokrinologie
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie
• Themenwelt: Naturwissenschaften ► Biologie ► Biochemie
• Themenwelt: Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie
• Themenwelt: Technik
• ISBN-10: 0-08-045804-1 / 0080458041
• ISBN-13: 978-0-08-045804-5 / 9780080458045